Risk Factors for Prostate Cancer

Screening for prostate cancer: protocol for updating multiple systematic reviews to inform a Canadian Task Force on Preventive Health Care guideline update

Article

Full-text available

Oct 2022

Purpose To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for prostate cancer in adults aged 18 years and older in primary care. This protocol outlines the planned scope and methods for a series of systematic reviews. Methods Updates of two systematic reviews and a de novo review will be conducted to synthesize the evidence on the benefits and harms of screening for prostate cancer with a prostate-specific antigen (PSA) and/or digital rectal examination (DRE) (with or without additional information) and patient values and preferences. Outcomes for the benefits of screening include reduced prostate cancer mortality, all-cause mortality, and incidence of metastatic prostate cancer. Outcomes for the harms of screening include false-positive screening tests, overdiagnosis, complications due to biopsy, and complications of treatment including incontinence (urinary or bowel), and erectile dysfunction. The quality of life or functioning (overall and disease-specific) and psychological effects outcomes are considered as a possible benefit or harm. Outcomes for the values and preferences review include quantitative or qualitative information regarding the choice to screen or intention to undergo screening. For the reviews on benefits or harms, we will search for randomized controlled trials, quasi-randomized, and controlled studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. For the review on values and preferences, we will search for experimental or observational studies in MEDLINE, Embase, and PsycInfo. For all reviews, we will also search websites of relevant organizations, gray literature, and reference lists of included studies. Title and abstract screening, full-text review, data extraction, and risk of bias assessments will be completed independently by pairs of reviewers with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of the evidence for each outcome. Discussion The series of systematic reviews will be used by the Canadian Task Force on Preventive Health Care to update their 2014 guideline on screening for prostate cancer in adults aged 18 years and older. Systematic review registration This review has been registered with PROSPERO (CRD42022314407) and is available on the Open Science Framework (osf.io/dm32k).

Un Vistazo al Cáncer de Próstata para un Diagnóstico Oportuno

Article

Full-text available

Jul 2022

Alexa María Marín Cascante

El cáncer de próstata es la neoplasia más frecuente en hombres alrededor del mundo, por lo que se necesita estar atentos para poder detectarlo a tiempo. Esto se logra realizando el tamizaje con el antígeno prostático específico, en pacientes mayores de 50 años y que presenten factores de riesgo, el cual tiene una alta sensibilidad pero una baja especificidad, por esto hay que saber cuáles son los factores pueden elevarlo y cuales pueden disminuirlo, afectando el diagnóstico oportuno que se puede dar. Además se debe de realizar un estadiaje clínico y patológico, para que el urólogo pueda dar un tratamiento adecuado según el estadio de su enfermedad, el estado funcional del paciente y sus necesidades.

Screening for prostate cancer: protocol for updating multiple systematic reviews to inform a Canadian Task Force on Preventive Health Care guideline update

Preprint

Full-text available

Mar 2022

Purpose: To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for prostate cancer in adults aged 18 years and older in primary care. This protocol outlines the planned scope and methods for a series of systematic reviews. Methods: Updates of two systematic reviews and a de novo review will be conducted to synthesize the evidence on the benefits and harms of screening for prostate cancer with prostate specific antigen (PSA) and/or digital rectal examination (DRE) (with or without additional information) and patient values and preferences. Outcomes for the benefits of screening include reduced prostate cancer mortality, all-cause mortality, and incidence of metastatic prostate cancer. Outcomes for the harms of screening include false positive screening tests, overdiagnosis, complications due to biopsy, and complications of treatment including incontinence (urinary or bowel), and erectile dysfunction. Quality of life or functioning (overall and disease-specific) and psychological effects outcomes are considered as a possible benefit or harm. Outcomes for the values and preferences review include quantitative or qualitative information regarding choice to screen or intention to undergo screening. For the reviews on benefits or harms, we will search for randomized controlled trials, quasi-randomised, and controlled studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. For the review on values and preferences, we will search for experimental or observational studies in MEDLINE, Embase, and PsycInfo. For all reviews, we will also search websites of relevant organizations, grey literature, and reference lists of included studies. Title and abstract screening, full-text review, data extraction, and risk of bias assessments will be completed independently by pairs of reviewers with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of the evidence for each outcome. Discussion: The series of systematic reviews will be used by the Canadian Task Force on Preventive Health Care to update their 2014 guideline on screening for prostate cancer in adults aged 18 years and older. Systematic review registration: This review has been registered with PROSPERO (ref# pending) and is available on the Open Science Framework (osf.io/dm32k).

Unveiling the Dual Threat: How Microbial Infections and Healthcare Deficiencies Fuel Cervical and Prostate Cancer Deaths in Africa

Article

Full-text available

Mar 2024

Cervical and prostate cancer account for 7.1 and 7.3 deaths per 100,000 people globally in 2022. These rates increased significantly to 17.6 and 17.3 in Africa, respectively, making them the second and third leading cause of cancer deaths in Africa, only surpassed by breast cancer. The human papillomavirus is the prime risk factor for cervical cancer infection. On the other hand, pros-tate cancer risks include ageing, genetics, race, geography, and family history. However, these factors alone cannot account for the high mortality rate in Africa, which is more than twice the global mortality rate for the two cancers. We searched PubMed, Embase, Scopus, and Web of Science to select relevant articles using keywords related to microorganisms involved in cervical and prostate cancer and the impact of poor healthcare systems on the mortality rates of these two cancers in Africa by carrying out a detailed synopsis of the studies on microbial agents involved and the contributory factors to the deteriorating healthcare system in Africa. It became apparent that the developed countries come first in terms of the prevalence of cervical and prostate cancer. However, more people per capita in Africa die from these cancers as compared to other continents. Also, microbial infections (bacterial or viral), especially sexually transmitted infections, cause inflammation, which triggers the pathogenesis and progression of these cancers among the African population; this has been linked to the region's deficient health infrastructure, making it difficult for people with microbial infections to access healthcare and hence making infection control and prevention challenging. Taken together, untreated microbial infections, primarily sexually transmitted infections due to the deficient healthcare systems in Africa, are responsible for the high mortality rate of cervical and prostate cancer.

Article

May 2024

Objective: To investigate the factors affecting patient satisfaction in patients undergoing prostate biopsy. Material and Methods: Two hundred thirty seven of 241 patients, aged between 48 and 86, those who are decided to undergo transrectal ultrasonography (TRUS)-guided prostate biopsy, were evaluated prospectively. Age, body mass index (BMI), prostate-specific antigen (PSA) values, prostate volume, positive digital rectal examination (DRE) findings and biopsy indications of the patients were recorded before the procedure. The level of pain felt during biopsy was scored by visualised pain scoring (VAS). Patient satisfaction was evaluated with a 4-point scale after biopsy. Results: Of the 237 patients evaluated, 92 were dissatisfied with the procedure, while 145 were satisfied. The mean age of Group 1 and Group 2 were 65.9±8.1 and 66.1 ± 7.6 years, BMI were 27.7±4.0 and 26.3 ± 3.9 kg/m2, PSA level were 58.6 ± 304.6 and 17.9 ± 68.1 ng/ml, Prostate volüme were 59.4 ± 51.8 and 51.8 ± 28.7 cc., The median VAS score 4 (3-6) and 4 (2.5-6) respectively. The Satisfaction levels of positive DRE findings Group was 3 (2-3) while negative 3 (2-3), Tumor existance Group was 3 (2-3) while no tumor Group’s Satisfaction levels 3 (2-3), Perineural invasion of tumor existance Group was 3 (2-3) while other Group’s Satisfaction levels 3 (2-3). Conclusion: In TRUS-guided prostate biopsies, no relationship was found between the patient’s satisfaction level and the patient’s age, PSA level, prostate volume, the level of pain felt, positive DRE finding, positive Tumor pathology or having perineural invasion of the tumor histologically. There is a statistically significant relationship between BMI and the level of satisfaction.

Critical Molecular Factors and Side Effects Underlying the Response to Thalicthuberine in Pros-tate Cancer: A Systems Biology Approach

Article

Full-text available

Jun 2022

Background: Uncontrolled mitosis of cancer cells and resistance cells to chemotherapy drugs are the challenges of prostate cancer. Thalicthuberine causes a mitotic arrest and a reduction of the effects of drug resistance, resulting in cell death. In this study, we applied bioinformatics and computational biology methods to identify functional pathways and side effects in response to Thalicthuberine in prostate cancer patients. Methods: Microarray data were retrieved from Gene Expression Omnibus (GEO), and protein-protein interactions and gene regulatory networks were constructed, using the Cytoscape software. The critical genes and molecular mechanisms in response to Thalicthuberine and its side effects were identified, using the Cytoscape software and WebGestalt server, respectively. Finally, GEPIA2 was used to predict the relationship between critical genes and prostate cancer. Results: The POLQ, EGR1, CDKN1A, FOS, MDM2, CDC20, CCNB1, and CCNB2 were identified as critical genes in response to this drug. The functional mechanisms of Thalicthuberine include a response to oxygen levels, toxic substances and immobiliza-tion stress, cell cycle regulation, regeneration, the p53 signaling pathway, the action of the parathyroid hormone, and the FoxO signaling pathway. Besides, the drug has side effects including muscle cramping, abdominal pains, paresthesia, and metabolic diseases. Conclusion: Our model suggested newly predicted crucial genes, molecular mechanisms , and possible side effects of this drug. However, further studies are required.

Machine learning pipeline to analyze clinical and proteomics data: experiences on a prostate cancer case

Article

Full-text available

Apr 2024
BMC MED INFORM DECIS

Proteomic-based analysis is used to identify biomarkers in blood samples and tissues. Data produced by devices such as mass spectrometry requires platforms to identify and quantify proteins (or peptides). Clinical information can be related to mass spectrometry data to identify diseases at an early stage. Machine learning techniques can be used to support physicians and biologists in studying and classifying pathologies. We present the application of machine learning techniques to define a pipeline aimed at studying and classifying proteomics data enriched using clinical information. The pipeline allows users to relate established blood biomarkers with clinical parameters and proteomics data. The proposed pipeline entails three main phases: (i) feature selection, (ii) models training, and (iii) models ensembling. We report the experience of applying such a pipeline to prostate-related diseases. Models have been trained on several biological datasets. We report experimental results about two datasets that result from the integration of clinical and mass spectrometry-based data in the contexts of serum and urine analysis. The pipeline receives input data from blood analytes, tissue samples, proteomic analysis, and urine biomarkers. It then trains different models for feature selection, classification and voting. The presented pipeline has been applied on two datasets obtained in a 2 years research project which aimed to extract hidden information from mass spectrometry, serum, and urine samples from hundreds of patients. We report results on analyzing prostate datasets serum with 143 samples, including 79 PCa and 84 BPH patients, and an urine dataset with 121 samples, including 67 PCa and 54 BPH patients. As results pipeline allowed to identify interesting peptides in the two datasets, 6 for the first one and 2 for the second one. The best model for both serum (AUC=0.87, Accuracy=0.83, F1=0.81, Sensitivity=0.84, Specificity=0.81) and urine (AUC=0.88, Accuracy=0.83, F1=0.83, Sensitivity=0.85, Specificity=0.80) datasets showed good predictive performances. We made the pipeline code available on GitHub and we are confident that it will be successfully adopted in similar clinical setups.

Prediction of Prostate Cancer Risk Stratification Based on A Nonlinear Transformation Stacking Learning Strategy

Article

Mar 2024
Int Neurourol J

Purpose: Prostate cancer (PCa) is an epithelial malignancy that originates in the prostate gland and is generally categorized into low, intermediate, and high-risk groups. The primary diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values. However, reliance on PSA levels can result in false positives, leading to unnecessary biopsies and an increased risk of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method for PCa risk stratification. Many recent studies on PCa risk stratification based on clinical data have employed a binary classification, distinguishing between low to intermediate and high risk. In this paper, we propose a novel machine learning (ML) approach utilizing a stacking learning strategy for predicting the tripartite risk stratification of PCa.Methods: Clinical records, featuring attributes selected using the lasso method, were utilized with 5 ML classifiers. The outputs of these classifiers underwent transformation by various nonlinear transformers and were then concatenated with the lasso-selected features, resulting in a set of new features. A stacking learning strategy, integrating different ML classifiers, was developed based on these new features.Results: Our proposed approach demonstrated superior performance, achieving an accuracy of 0.83 and an area under the receiver operating characteristic curve value of 0.88 in a dataset comprising 197 PCa patients with 42 clinical characteristics.Conclusions: This study aimed to improve clinicians’ ability to rapidly assess PCa risk stratification while reducing the burden on patients. This was achieved by using artificial intelligence-related technologies as an auxiliary method for diagnosing PCa.

Cancer Theranostics: Pharmaceutical View

Chapter

Full-text available

Mar 2024

Cancer is undeniably a scary disease that leads to morbidity and mortality. With the state-of-the-art advances, chemotherapy has made incredible strides, but the efficiency is still questionable. Diagnosing and treating cancer are necessary to effectively approach the disease. Theranostics is a hybrid technique that combines therapeutics and diagnostics. The key to cancer therapy is targeted drug delivery, which specifically kills cancer cells without harming healthy cells. The idea of targeted therapy is merely a theoretical expectation that the drug will reach the target site. As seeing is believing, theranostics helps visualize the drug delivery with the combination of diagnostic agents. Clinical settings have extensively examined the field of theranostics. This chapter goes into great length about the potential targets and radioisotopes in theranostics.

Omics sciences and precision medicine in prostate cancer

Article

Full-text available

Nov 2023

In the last decade, Prostate Cancer (PCa) has emerged as the second most prevalent and serious medical condition, and is considered one of the leading factors contributing to global mortality rates. Several factors (genetic as well as environmental) contribute to its development and seriousness. Since the disease is usually asymptomatic at early stages, it is typically misdiagnosed or over-diagnosed by the diagnostic procedures currently in use, leading to improper treatment. Effective biomarkers and diagnostic techniques are desperately needed in clinical settings for better management of PCa patients. Studies integrating omics sciences have shown that the accuracy and dependability of diagnostic and prognostic evaluations have increased because of the use of omics data; also, the treatment plans using omics can be facilitated by personalized medicine. The present review emphasizes innovative multi-omics metho-dologies, encompassing proteomics, genomics, microbiomics, me-tabolomics, and transcriptomics, with the aim of comprehending the molecular alterations that trigger and contribute to PCa. The review shows how early genomic and transcriptomic research has made it possible to identify PCa-related genes that are controlled by tumor-relevant signaling pathways. Proteomic and metabolomic analyses have recently been integrated, advancing our understanding of the complex mechanisms at play, the multiple levels of regulation, and how they interact. By applying the omics approach, new vulnerabilities may be discovered, and customized treatments with improved efficacy will soon be accessible.

HMARNET—A Hierarchical Multi‐Attention Residual Network for Gleason scoring of prostate cancer

Article

Full-text available

Oct 2023
INT J IMAG SYST TECH

Manual delineation of prostate cancer (PCa) from whole slide images (WSIs) demands requires pathologists with adequate domain knowledge. This process is generally strenuous and may be subjected to poor inter‐pathologist reproducibility. Accurate Gleason scoring is an important step in the computer‐aided diagnosis of PCa. This work proposes a novel lightweight convolutional neural networks (CNN) to extract significant hierarchical features from the histopathology images. It learns meticulous attention‐guided feature representations through the convolutional layers for precise scoring of Gleason grades. The Hierarchical Multi‐Attention Residual (HMAR) block extracts attention‐guided features and fuses the resulting feature maps from multiple levels with a reduced number of trainable parameters. We have also proposed a new lightweight channel‐attention module, enhanced channel attention (ECA) to extract inter‐channel features from different receptive fields. With the presence of different attention mechanisms, the network learns to focus on more significant features rather than unnecessary ones. Additionally, mixed FocalOHEM loss is proposed to optimize the CNN and efficiently minimize the error. While the focal loss helps to address the class imbalance present in the TCGA‐PRAD dataset, the online hard example mining (OHEM) loss focuses on optimizing hard negative samples. It achieved an accuracy of 89.19% with a Kappa score of 86% on the TCGA‐PRAD dataset.

Intranasal drug delivery system for treatment of cancer’

Chapter

Full-text available

Sep 2023

Neelam Singh

Gene Drug Delivery for the Treatment of cancer

Chapter

Full-text available

Nov 2023

Neelam Singh

Machine Learning Pipeline to analyze Clinical and Proteomics Data: experiences on a prostate cancer case

Preprint

Full-text available

Aug 2023

Proteomic-based analysis is used to identify biomarkers in blood samples and tissues. Data produced by devices such as mass spectrometry, requires platforms to identify and quantify proteins (or peptides). Clinical information can be related with mass spectrometry data to identify diseases at an early stage. Machine learning techniques can be used to support physicians and biologists for studying and classifying pathologies. We present the application of machine learning techniques to define a pipeline aimed to study and classify protemics data enriched by means of clinical information. The pipeline allows users to relate established blood biomarkers with clinical parameters and proteomics data. The proposed pipeline entails three main phases: (i) feature selection, (ii) models training and (iii) models ensembling. We report the experience of applying such a pipeline on prostate related diseases. Models have been trained on a datasets which results from the integration of clinical and mass spectrometry based data. The pipeline receives as input data from blood analytes, tissue samples, proteomic analysis and urine biomarkers. It then learns different models for feature selection and classification.The presented pipeline has been applied on two datasets onbtained a 2 years research project which aimed to extract hidden information from mass spectrometry, serum and urine samples from hundreds of patients. We report results on analyzing prostate datasets with 163 samples, including 79 patient, and a urine dataset with 121 patients. As results pipeline allowed to identify interesting peptides in the two datasets, 6 for the first one and 2 for the second one. The best model for both prostate (AUC=0.815, F1=0.8, Specificity=0.75, Sensitivity=0.88) and urine (AUC=0.810, F1=0.824, Specificity=0.805, Sensitivity=0.814) datasets showed good predictive performances.We are confident that the pipeline can be successfully adopted in similar clinical setups.

Debating Prostate Cancer in Cisgender Men and Transgender Women

Article

Full-text available

Jan 2023

Prostate cancer is considered the second most prevalent type of cancer in men and the fifth leading cause of death worldwide. Although there are programs aimed at this problem, their scope is still limited due to inequity of sex, gender and sexual orientation, highlighting the need for actions that reach both cis men and trans women. Therefore, the objective was to critically reflect on preventive campaigns on Prostate Cancer in cisgender men and transgender women. The theoretical reflection method was adopted, initially through the search and reading of articles, followed by the problematization of the findings, with emphasis on the main concepts and actions developed in Brazil on the subject. The epidemiological and political context and the need for change in the health care of that population were highlighted, which indicate the need for a new look at this public and the effectiveness of the actions that are carried out.

Detection of high-risk Human Papillomavirus in prostate cancer from a UK based population

Article

Full-text available

May 2023

Human papillomavirus (HPV) infection is one of the sexually transmitted diseases which have been implicated in the etiology of multiple cancers. To date, several studies have been conducted to evaluate the incidence of high-risk (HR) HPV in prostate cancer (PCa) which have generated widely conflicting data. Hence, this leaves a lack of awareness on the causal role of persistent HPV infection in the development of PCa. Although this has been investigated in a handful of countries, to the best of our knowledge, no prior studies have been conducted in the UK. In this study, polymerase chain reaction (PCR) and Sanger sequencing were implemented to analyze a total of 49 fresh prostate specimens (35 benign and 14 malignant specimens) for the presence of viral DNA of 12 HR-HPV types. Data obtained confirmed the presence of HR-HPV in 32.7% of analyzed benign and malignant prostate tissues with HPV 35 being identified as the most frequent type. Moreover, HR-HPV positivity rate was found to be higher in abnormal prostate tissues (adenocarcinoma and benign with prostatitis) compared those with normal prostate condition. Using immunohistochemistry, we have confirmed the expression of HPV E7 protein in prostate tissues positive for HPV DNA. This observation, the first reported from a UK population, suggests that the presence of HPV in prostate tissue is likely to be a related factor in the progression of certain cases of prostate cancer.

Study on Early Prostate Cancer Antigen (EPCA) and existent risk factors of prostate cancer, Sudan: A case-control study

Article

Full-text available

Feb 2023

Elhadi Ahmed

Background: Early prostate cancer antigen (EPCA), a nuclear matrix protein, has recently been recommended as a hopeful biomarker for early prostate carcinogenesis. Objectives: To evaluate the validity of serum early prostate cancer antigen (EPCA) in the early detection of prostate cancer (PCa) and the characteristics of Sudanese patients diagnosed with prostate cancer. Method: In this study, seventy men were considered as a case subject, who were diagnosed as cancer prostate at Gezira Hospital for Renal Disease and Surgery (GHRDS), Sudan during the period February 2018 to July 2019. Randomly selected sixty patients of BPH patients and forty-five apparently healthy men as controls group. EPCA, and PSA estimations were performed from serum samples using the principle of Enzyme Linked Immunosorbent Assay (ELISA). Results: There was significant association between age, family history, residence, unhealthy habits, education, BMI, occupations and prostate cancer, results also revealed a significant elevation between the means of the serum levels of both early prostate cancer antigen and prostate specific antigen of the patients with prostate cancer when compared with the control groups. EPCA biomarker offered the best performance statically (P= 0.00) and highest specificity (81%) and sensitivity (94%) in prostate cancer detection in Sudanese males over PSA biomarker. Conclusions: Cases of studied prostate cancer linked to many risk factors. Serum levels of early prostate cancer antigen and prostate specific antigen were significantly increased in patients with prostate cancer, however, our data proposed that EPCA has higher power statistical value, so could be utilized as a prostate cancer speciﬁc and sensitive biomarker for early detection of prostate cancer.

A Survey of Knowledge of and Attitudes towards Prostate Cancer Among a Sample of Nigeria Men

Article

Full-text available

Jan 2021

Abstract The prevalence of non-communicable diseases (NCD), including cancer, are surpassing that of infectious disease as the leading healthcare threat in some middle income and low-income countries around the globe. Aim: This study sought to know the level of knowledge of and attitude towards prostate cancer among men. Methods: A descriptive cross-sectional study was conducted on a random sample of 1025 men, who gathered for a health seminar at a national convention. A questionnaire that contained questions on the knowledge of men and their attitude towards PCa and its risk factors was administered. Data were analyzed using descriptive and inferential statistics. Results: 436(42.6%) of respondents had heard about the PCa and 373 (36.4%) had heard about PSA-test. Social and electronic (radio/television) media constituted greater sources of information for 399 (39%) and 556 (54.2%) respectively who have heard about PCa. The level of knowledge was higher in men with higher education level, older and with relatives or friends with prostate problems or cancers. 199(19.4%) of the respondents had carried out the PCa test, while 817(79.7%) indicated an interest in undergoing the test after the seminar. Determination to undertake a PSA test was associated with a higher level of education (p=0.026) and older age (p=0.031) among those who have received information from their doctors (p=0.019) and those already experiencing signs of ill-health (p=0.040). Conclusion: There was a low level of knowledge among the respondents. The study, therefore, suggested the need for increased public awareness and education on the risks of prostate cancer and the benefits of its prevention.

A systematic review on the association between ovarian and prostate cancer with BRCA1 and BRCA2 gene

Article

Full-text available

Jan 2023

Background . BRCA1 and BRCA2 were discussed as the basis of inherited adenocarcinoma and breast and ovarian malignancy. Ovarian cancer is uncommon in women below 40 years of age, and prostate cancer mainly occurs in older men cause 90 % in those above sixty-fve. Objective . The main objective of this paper is to investigate the relationship between ovarian and prostate cancer with the BRCA1 and BRCA2 genes. Material and Methods . The ovarian and prostate cancer mechanism is discussed in detail, and their preventive measures with screening techniques are also demonstrated. This systematic review collected the related articles from online databases using the key terms ovarian cancer, prostate cancer, BRCA genes, mutation, polymorphism, carcinoma, sarcoma, and genetic association. Results . Based on the obtained information, it is found that the BRCA genes are highly associated with prostate cancer in men, and in women, it is significantly linked with breast cancer than ovarian cancer. Conclusion . Therefore, early diagnosis and genetic testing for BRCA1&BRCA2 genes in both men and women are necessary. In some cases, these genes might even cause different types of cancer like pancreatic cancers. Identifying individuals with tumour-HRD through mutations in the homologous repair pathway and determining this gene expression is essential to improve treatment techniques developed during the previous decade and rapidly make their way into clinical trials practice. However, the safe introduction of these medicines into everyday practice will require a thorough understanding of treatment targets and associated adverse effects.

Identification of Critical Molecular Factors and Side Effects Underlying the Response to Thalicthuberine in Prostate Cancer: A Systems Biology Approach

Article

Full-text available

Dec 2022

Background: Uncontrolled mitosis of cancer cells and resistance cells to chemotherapy drugs are the challenges of prostate cancer. Thalicthuberine causes a mitotic arrest and a reduction of the effects of drug resistance, resulting in cell death. In this study, we applied bioinformatics and computational biology methods to identify functional pathways and side effects in response to Thalicthuberine in prostate cancer patients. Methods: Microarray data were retrieved from Gene Expression Omnibus (GEO), and protein-protein interactions and gene regulatory networks were constructed, using the Cytoscape software. The critical genes and molecular mechanisms in response to Thalicthuberine and its side effects were identified, using the Cytoscape software and WebGestalt server, respectively. Finally, GEPIA2 was used to predict the relationship between critical genes and prostate cancer. Results: The POLQ, EGR1, CDKN1A, FOS, MDM2, CDC20, CCNB1, and CCNB2 were identified as critical genes in response to this drug. The functional mechanisms of Thalicthuberine include a response to oxygen levels, toxic substances and immobilization stress, cell cycle regulation, regeneration, the p53 signaling pathway, the action of the parathyroid hormone, and the FoxO signaling pathway. Besides, the drug has side effects including muscle cramping, abdominal pains, paresthesia, and metabolic diseases. Conclusion: Our model suggested newly predicted crucial genes, molecular mechanisms, and possible side effects of this drug. However, further studies are required.

LINC00893 inhibits the progression of prostate cancer through miR-3173-5p/SOCS3/JAK2/STAT3 pathway

Article

Full-text available

Jul 2022
Canc Cell Int

Background Prostate cancer (PCa) is one of the most common malignant tumors in the male urinary system. In recent years, the morbidity and mortality of PCa have been increasing due to the limited effects of existing treatment strategies. Long non-coding RNA (lncRNA) LINC00893 was reported to inhibit the proliferation and metastasis of papillary thyroid cancer cells, but its role in PCa has not been reported. This study aims to investigate the role and underlying mechanism of LINC00893 in regulating the progression of PCa cells. Methods We first compared LINC00893 expression levels between PCa tissues and normal prostate tissues through TCGA database. The relative LINC00893 expression levels were further validated in 66 pairs of PCa tissues and para-cancerous normal tissues, as well as in PCa cell lines. Gain-of-function experiment was performed by transfecting PCa cell with LINC00893 expression vector, and CCK (Cell count kit)-8, 5-Ethynyl-2′-deoxyuridine (EdU) incorporation, colony information and transwell assays were conducted to assess the functional phenotypes. Dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP) and RNA pull-down assays were performed to evaluate the molecular interactions. Results LINC00893 was downregulated in PCa tissues and cell lines, and patients with low expression of LINC00893 were associated with a poorer overall survival rate. LINC00893 overexpression hindered the proliferation, epithelial-mesenchymal transition (EMT) as well as the migratory ability of PCa cells, and suppressed the tumorigenesis of PCa cells in nude mice. We further demonstrated that LINC00893 acted as a sponge for miR-3173-5p and inhibited its activity, which in turn regulated the suppressor of cytokine signaling 3 (SOCS3)/Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling axis. Conclusions Our study demonstrated that LINC00893 suppresses the progression of PCa cells through targeting miR-3173-5p/SOCS3/JAK2/STAT3 axis. Our data uncovers a novel tumor-suppressor role of LINC00893 in PCa, which may serve as a potential strategy for targeted therapy in PCa. Grapical Abstract

Discriminatory Gleason grade group signatures of prostate cancer: An application of machine learning methods

Article

Full-text available

Jun 2022
PLOS ONE

One of the most precise methods to detect prostate cancer is by evaluation of a stained biopsy by a pathologist under a microscope. Regions of the tissue are assessed and graded according to the observed histological pattern. However, this is not only laborious, but also relies on the experience of the pathologist and tends to suffer from the lack of reproducibility of biopsy outcomes across pathologists. As a result, computational approaches are being sought and machine learning has been gaining momentum in the prediction of the Gleason grade group. To date, machine learning literature has addressed this problem by using features from magnetic resonance imaging images, whole slide images, tissue microarrays, gene expression data, and clinical features. However, there is a gap with regards to predicting the Gleason grade group using DNA sequences as the only input source to the machine learning models. In this work, using whole genome sequence data from South African prostate cancer patients, an application of machine learning and biological experiments were combined to understand the challenges that are associated with the prediction of the Gleason grade group. A series of machine learning binary classifiers (XGBoost, LSTM, GRU, LR, RF) were created only relying on DNA sequences input features. All the models were not able to adequately discriminate between the DNA sequences of the studied Gleason grade groups (Gleason grade group 1 and 5). However, the models were further evaluated in the prediction of tumor DNA sequences from matched-normal DNA sequences, given DNA sequences as the only input source. In this new problem, the models performed acceptably better than before with the XGBoost model achieving the highest accuracy of 74 ± 01, F1 score of 79 ± 01, recall of 99 ± 0.0, and precision of 66 ± 0.1.

Carriage of mutations R462Q (rs 486907) and D541E (rs 627928) of the RNASEL gene and risk factors in patients with prostate cancer in Burkina Faso

Article

Full-text available

Jun 2022
BMC MED GENOMICS

Background Prostate cancer (Pca) is a public health problem that affects men, usually of middle age or older. It is the second most common cancer diagnosed in men and the fifth leading cause of death. The RNASEL gene located in 1q25 and identified as a susceptibility gene to hereditary prostate cancer, has never been studied in relation to prostate cancer in Burkina Faso. The aim of this study was to analyze the carriage of RNASEL R462Q and D541E mutations and risks factors in patients with prostate cancer in the Burkina Faso. Methods This case–control study included of 38 histologically diagnosed prostate cancer cases and 53 controls (cases without prostate abnormalities). Real-time PCR genotyping of R462Q and D541E variants using the TaqMan® allelic discrimination technique was used. Correlations between different genotypes and combined genotypes were investigated. Results The R462Q variant was present in 5.3% of cases and 7.5% of controls. The D541E variant was present in 50.0% of cases and 35% of controls. There is no association between R462Q variants (OR = 0.60; 95%IC, 0.10–3.51; p = 0.686) and D541E variants (OR = 2.46; 95%IC, 0.78–7.80; p = 0.121) and genotypes combined with prostate cancer. However, there is a statistically significant difference in the distribution of cases according to the PSA rate at diagnosis (p ˂ 0.001). For the Gleason score distribution, only 13.2% of cases have a Gleason score greater than 7. There is a statistically significant difference in the Gleason score distribution of cases (p ˂ 0.001). Conclusions These variants, considered in isolation or in combination, are not associated with the risk of prostate cancer.

PROSTATE SPECIFIC ANTIGEN IN PATIENTS OF BENIGN PROSTATE HYPERTROPHY AND CARCINOMA PROSTATE

Article

Full-text available

Jan 2006
Indian J Clin Biochem

Prostate Specific Antigen (PSA) has emerged as the most applicable and important tumor marker for carcinoma prostate. In the present study PSA was determined in serum of healthy subjects, patients of benign prostate hypertrophy (BPH) and Carcinoma Prostate (Ca-P) to evaluate its diagnostic efficiency in day to day management of prostate cancer patients and in differentiating patients of early prostate cancer from those with BPH. Receiver operating characteristic curve (ROC) revealed 2 ng/ml and 10 ng/ml cut off serum PSA level for BPH and untreated carcinoma prostate patients (Ca-P). An extremely significant increase (P<0.0001) was observed in mean PSA concentration in BPH patients and adenocarcinoma prostate patients when compared to healthy males. Clinical relevance of PSA was highlighted by a case study of cancer patient prior to any therapy till death.

Ex Vivo High-Resolution Magic Angle Spinning (HRMAS) 1H NMR Spectroscopy for Early Prostate Cancer Detection

Article

Full-text available

Apr 2022

Simple Summary Prostate cancer is the second leading cancer diagnosed in men worldwide. Current diagnostic standards lack sufficient reliability in detecting and characterizing prostate cancer. Due to the cancer’s multifocality, prostate biopsies are associated with high numbers of false negatives. Whereas several studies have already shown the potential of metabolomic information for PCa detection and characterization, in this study, we focused on evaluating its predictive power for future PCa diagnosis. In our study, metabolomic information differed substantially between histobenign patients based on their risk for receiving a future PCa diagnosis, making metabolomic information highly valuable for the individualization of active surveillance strategies. Abstract The aim of our study was to assess ex vivo HRMAS (high-resolution magic angle spinning) ¹H NMR spectroscopy as a diagnostic tool for early PCa detection by testing whether metabolomic alterations in prostate biopsy samples can predict future PCa diagnosis. In a primary prospective study (04/2006–10/2018), fresh biopsy samples of 351 prostate biopsy patients were NMR spectroscopically analyzed (Bruker 14.1 Tesla, Billerica, MA, USA) and histopathologically evaluated. Three groups of 16 patients were compared: group 1 and 2 represented patients whose NMR scanned biopsy was histobenign, but patients in group 1 were diagnosed with cancer before the end of the study period, whereas patients in group 2 remained histobenign. Group 3 included cancer patients. Single-metabolite concentrations and metabolomic profiles were not only able to separate histobenign and malignant prostate tissue but also to differentiate between samples of histobenign patients who received a PCa diagnosis in the following years and those who remained histobenign. Our results support the hypothesis that metabolomic alterations significantly precede histologically visible changes, making metabolomic information highly beneficial for early PCa detection. Thanks to its predictive power, metabolomic information can be very valuable for the individualization of PCa active surveillance strategies.

Survival Prediction for Prostate Cancer Using Machine Learning and Bioinformatics Models

Conference Paper

Full-text available

Dec 2021

Case Study of Noni Extract in Men with Very Low-Risk or Low-Risk Prostate Cancer

Article

Oct 2021

The optimal treatment strategy for patients with early prostate cancer (PCa) is unknown. We explored the feasibility of administering noni supplementation to modify gene expression of a relevant clinical signature in the prostate of men on active surveillance for PCa. A total of 6 participants with low-risk (n=5) to very low-risk (n=1) PCa who were candidates for active surveillance received 6200 mg/day of noni in capsule form for 1 year; median age was 65.5 years (range, 58-75 years). Participants were tested for serum prostate-specific antigen (PSA) levels every 3 months. At 12 months, they underwent a repeat transrectal ultrasound-guided prostate biopsy. These biopsy samples were queried for expressing 12 key genes and rates of apoptosis, angiogenesis, and proliferation. The primary outcome was the change in expression of the 12 genes that comprise the Oncotype DX prostate cancer test from baseline to 12 months of noni supplementation. Noni was well tolerated, with only 1 participant reporting side effects of grade 2 diarrhea, requiring a drug holiday of 7 days. Median serum PSA slightly increased from 7.1 ng/mL (4.4-9.7 ng/ mL) prior to therapy to 7.9 ng/mL (5.7-10.2 ng/mL) on therapy. Changes were observed in the expression levels of several genes, including FAM13C, KLK2 (associated with the androgen pathway), and GSTM2 (associated with cellular organization) at 12 months. Noni supplementation was associated with favorable clinical parameters, including stable serum PSA among most patients and no evidence of tumor on repeat biopsy, and correlated with modulation of numerous genes and proteins.

A Comprehensive Evaluation of Health-Related Life Quality Assessment Through Head and Neck, Prostate, Breast, Lung, and Skin Cancer in Adults

Article

Full-text available

Apr 2022

Health assessment data assists the well-being and patient care teams' process in drawing up a care and assistance plan and comprehending the requirements of the patient. Comprehensive and precise data about the Quality of Life of cancer patients play a significant part in the development and organization of cancer patient care. Quality of Life has been used to mean a variety of various things, such as health situation, physical function, symptoms, psychosocial modification, well-being, enjoyment of life, and happiness. Chronic diseases such as cancer are among the disorders that severely affect people's health and consequently their Quality of Life. Cancer patients experience a range of symptoms, including pain and various physical and mental conditions that negatively affect their Quality of Life. In this article, we examined cancer and the impact that this disease can have on the Quality of Life of cancer patients. The cancers examined in this article include head and neck, prostate, breast, lung, and skin cancers. We also discussed health assessment and the importance and purpose of studying patients' Quality of Life, especially cancer patients. The various signs and symptoms of the disease that affect the Quality of Life of patients were also reviewed.

A protein coupling and molecular simulation analysis of the clinical mutants of Androgen receptor revealed a higher binding for Leupaxin, to increase the Prostate cancer invasion and motility

Article

Apr 2022
COMPUT BIOL MED

Recently a novel coactivator, Leupaxin (LPXN), has been reported to interact with Androgen receptor (AR) and play a significant role in the invasion and progression of prostate cancer. The interaction between AR and LPXN occurs in a ligand-dependent manner and has been reported that the LIM domain in the Leupaxin interacts with the LDB (ligand-binding domain) domain AR. However, no detailed study is available on how the LPXN interacts with AR and increases the (prostate cancer) PCa progression. Considering the importance of the novel co-activator, LPXN, the current study also uses state-of-the-art methods to provide atomic-level insights into the binding of AR and LPXN and the impact of the most frequent clinical mutations H874Y, T877A, and T877S on the binding and function of LPXN. Protein coupling analysis revealed that the three mutants favour the robust binding of LPXN than the wild type by altering the hydrogen bonding network. Further understanding of the binding variations was explored through dissociation constant prediction which demonstrated similar reports as the docking results. A molecular simulation approaches further revealed the dynamic features which reported variations in the dynamics stability, protein packing, hydrogen bonding network, and residues flexibility index. Furthermore, we also assessed the protein motion and free energy landscape which also demonstrated variations in the internal dynamics. The binding free energy calculation revealed -32.95±0.17 kcal/mol for the wild type, for H874Y the total binding energy (BFE) was -36.69±0.11 kcal/mol, for T877A the BFE was calculated to be -38.78±0.17 kcal/mol while for T877S the BFE -41.16±0.12 kcal/mol. This shows that the binding of LPXN is increased by these mutations which consequently increase the PCa invasion and motility. In conclusion, the current study helps in understanding the protein networks and particular the coupling of AR-LPXN in prostate cancer and is of great interest in deciphering the molecular mechanism of disease and therapeutics developments.

Racial Disparities in Prostate Cancer: Evaluation of Diet, Lifestyle, Family History, and Screening Patterns

Article

Mar 2022
CANCER EPIDEM BIOMAR

Background: Racial disparities in prostate cancer incidence and mortality rates are considerable. We previously found in the Health Professionals Follow-up Study (HPFS) that African American men had an 80% higher prostate cancer risk than white men. With 21 additional years of follow-up and four-fold increase in cases, we undertook a contemporary analysis of racial differences in prostate cancer incidence and mortality in HPFS. Methods: For 47,679 men, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between race and risk of prostate cancer through 2016 using Cox proportional hazards regression. Multivariable models adjusted for lifestyle, diet, family history, and PSA screening collected on biennial questionnaires. Results: 6,909 prostate cancer cases were diagnosed in white, 89 in African American, and 90 in Asian American men. African Americans had higher prostate cancer incidence (mHR 1.31, 95% CI 1.06-1.62) and mortality (mHR 1.67, 95% CI 1.00-2.78), and lower PSA screening prevalence than white men. The excess risk was greater in the pre-PSA screening era (HR 1.68, 95% CI 1.14-2.48) than the PSA screening era (HR 1.20, 95% CI 0.93-1.56). Asian Americans had lower prostate cancer risk (mHR 0.74, 95% CI 0.60-0.92), but similar risk of fatal disease compared to white men. Conclusions: Racial differences in prostate cancer incidence and mortality in HPFS are not fully explained by differences in lifestyle, diet, family history, or PSA screening. Impact: Additional research is necessary to address the disproportionately higher rates of prostate cancer in African American men.

Cancer Ther Oncol Int J Prostate Cancer Review Article

Article

Full-text available

Jun 2021

Prostate cancer is somewhat unusual when compared with other types of cancer. This is because many prostate tumors do not spread quickly to other parts of the body. Some prostate cancers grow very slowly and may not cause symptoms or problems for years or ever. Even when prostate cancer has spread to other parts of the body, it can be managed for a long time, allowing men even with advanced prostate cancer to live with good health and quality of life for many years. Vitamin D is a steroid hormone that is thought to play a role in the etiology and progression of prostate cancer. Hormone activity requires binding to the vitamin D receptor (VDR), which contains several genetic polymorphisms that have been associated with risk of prostate cancer

APAI POLYMORPHISM FREQUENCIES AND PROSTATE CANCER PATIENTS IN PUNJAB, PAKISTAN

Article

Full-text available

Feb 2022

Prostate cancer is the third most common malignancy in Pakistani males. Vitamin D receptor (VDR) gene has been a subject of extensive pharmacogenetic research recently. Association studies between different types of cancers including prostate cancer (PCa) and VDR gene polymorphism have also great importance. Vitamin D has an anticancer effect, so VDR gene polymorphisms have got much attention. It is proposed that vitamin D deficiency may underlie the major risk factors for prostate cancer, including age, black race and genetic variation in vitamin D-binding protein. Clinical diagnosis of prostate cancer can be done by PSA and biopsy. The clinical diagnosis does not provide a definitive diagnosis of progression of PCa. Most common symptoms of prostate cancer are Nocturia (increased urination at night), difficulty in urination, Hematuria (blood in urine), and Dysuria (frequent and painful urination). It may influence sexual function, for instance, trouble in accomplishing an erection or agonizing discharge. Advance prostate cancer may spread to other organs of the body, causing pain in pelvis or ribs. In Benign prostate hyperplasia, prostate enlarges and cause urinary symptoms. Diagnosis of prostate cancer can be done by needle biopsy or DRE (digital rectal examination). In benign prostatic hypertrophy/hyperplasia (BPH), prostate continues to enlarge over time. Prostate-specific antigen (PSA) is a glycoprotein, produced by epithelial prostate cells and is unique to the prostate gland. We found ApaI CC genotypes to increase the prostate cancer risk while CA and AA show less than 50% association with the disease. ApaI polymorphism has a strong correlation with PCa than TaqI. Different VDR gene polymorphisms seem to have an association with the PCa but not consistent with other ethnic groups

A systematic review of disease related stigmatization in patients living with prostate cancer

Article

Full-text available

Feb 2022
PLOS ONE

Background Prostate cancer has been shown to be susceptible to significant stigmatisation, because to a large extent it is concealable, it has potentially embarrassing sexual symptoms and has significant impact on the psychosocial functioning. Methods This review included studies that focused on qualitative and/or quantitative data, where the study outcome was prostate cancer and included a measure of stigmatization. Electronic databases (CINAHL, Medline, PubMed, PsycInfo, Cochrane Library, PROSPERO, and the Joanna Briggs Institute) and one database for grey literature Opengrey.eu , were screened. We used thematic analysis, with narrative synthesis to analyse these data. We assessed risk of bias in the included studies using the RoBANS. Results In total, 18 studies met review inclusion criteria, incorporating a total of 2295 participants. All studies recruited participants with prostate cancer, however four studies recruited participants with other cancers such as breast cancer and lung cancer. Of the 18 studies, 11 studies evaluated perceived or felt stigma; four studies evaluated internalised or self-stigma; three studies evaluated more than one stigma domain. Discussion We found that patients living with prostate cancer encounter stigmatisation that relate to perception, internalisation, and discrimination experiences. We also identified several significant gaps related to the understanding of prostate cancer stigmatization, which provides an opportunity for future research to address these important public health issues. Registration This systematic review protocol is registered with PROSPERO, the international prospective register of systematic reviews in health and social care. Registration number: CRD42020177312 .

Effect of pneumoperitoneum and Trendelenburg position on internal carotid artery blood flow measured by ultrasound during robotic prostatectomy

Article

Jan 2022
CLIN PHYSIOL FUNCT I

Introduction Robotic prostatectomy requires pneumoperitoneum and a steep Trendelenburg position; however, this condition may compromise cerebral blood flow. Here, we evaluated the effect of pneumoperitoneum and the steep Trendelenburg position on internal carotid artery (ICA) blood flow measured by Doppler ultrasound during robotic prostatectomy. Methods Patients who underwent robotic prostatectomy were prospectively recruited. The ICA blood flow was measured at the following five time-points: with the patient awake and in the supine position (Ta), 10 min after anaesthetic induction in the supine position (T1), 10 (T2) and 30 (T3) min after pneumoperitoneum in the steep Trendelenburg position, and at the end of surgery in the supine position after desufflation of the pneumoperitoneum (T4). Hemodynamic and cerebrovascular variables were measured at each time-point. Results A total of 28 patients were evaluated. The ICA blood flows were significantly lower at T2 and T3 than at T1 (162.3±44.7 [T2] vs. 188.0±49.6 mL/min [T1], P=0.002; 163.1±39.9 [T3] vs. 188.0±49.6 mL/min [T1], P=0.009). The ICA blood flow also differed significantly between Ta and T1 (236.8±58.3 vs. 188.0±49.6 mL/min, P<0.001). Heart rates, cardiac indexes, peak systolic velocity, and end-diastolic velocity were significantly lower at T2 and T3 than at T1. However, ICA diameter, mean blood pressure, and end-tidal carbon dioxide partial pressure did not differ significantly at all time-points. Conclusion Pneumoperitoneum and the steep Trendelenburg position caused decreased ICA blood flow, suggesting that they should be carefully performed during robotic prostatectomy, especially in patients at risk of postoperative cerebrovascular accident. This article is protected by copyright. All rights reserved.

The Important Role of TMPRSS2 Gene in Covid-19 and Prostate Cancer: In Silico Approach

Article

Full-text available

Nov 2021
BRAZ ARCH BIOL TECHN

Abstract Some studies have discovered a connection between prostate cancer and COVID-19. In this study, we evaluated the link between prostate cancer and COVID-19, contributing to elucidate the connection between TMPRSS2 and ACE2. We discovered 209 number of variants in TMPRSS2 gene, and 110 variants represent EA populations and 99 of them represent AA populations. Moreover, we found 23 suspected missense and 3 unknown variants. Then, linked genes to TMPRSS2 and ACE2 were found in our study. We investigated the expression level of TMPRSS2 and the results showed that it was very high in the prostate, colon, lung, kidney, and saliva-secreting gland. Also, the important role of the AR gene was revealed in addition to other oncogenes and tumor suppressor genes for prostate cancer by KEGG Pathway analysis. In conclusion, these results can highlight several molecular mechanisms of SARS-CoV-2, and also TMPRSS2, ACE2, and AR connection explains the high expression level of AR gene found in the male lung.

LINC00893 Inhibits The Progression of Prostate Cancer Through miR-3173-5p/SOCS3/JAK2/STAT3 Pathway

Preprint

Full-text available

Aug 2021

Background: Prostate cancer (PCa) is one of the most common malignant tumors in the male urinary system. In recent years, the morbidity and mortality of PCa have been increasing due to the limited effects of existing treatment strategies. Long non-coding RNA (lncRNA) LINC00893 inhibits the proliferation and metastasis of papillary thyroid cancer (PTC) cells, but its role in PCa has not been reported. Our study aims to clarify the role and underlying mechanism of LINC00893 in regulating the progression of PCa. Methods: We analyzed LINC00893 expression through TCGA database. We also collected 66 paires of PCa tissues and matched para-cancerous tissues as well as cell lines and assessed LINC00893 expression. Subsequently, we conducted gain-of-function assays to confirm the role of LINC00893 in PCa. CCK-8, EdU, colony information and transwell assays were implemented to detect cell proliferation, colony formation and metastasis abilities, respectively. RT-qPCR and western blot assays were used to quantify the expression of mRNA and protein. Dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP) and RNA pull down assays were conducted to evaluate the interaction of molecules. Spearman correlation coefficient analysis was conducted to detect the correlation between molecules. Results: We found that the LINC00893 expression in PCa tissues and cell lines was upregulated compared with matched controls, and patients with low expression of LINC00893 suffered a low overall survival rate. Overexpression of LINC00893 hindered the proliferation, epithelial-mesenchymal transition (EMT) as well as metastasis of PCa cells in vitro and in vivo. In terms of mechanism, suppressor of cytokine signaling 3 (SOCS3)/Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway occupied a central position in the regulation of PCa progression by LINC00893. LINC00893 weakened the inhibition role of miR-3173-5p on SOCS3 expression through functioning as a miR-3173-5p sponge, which inhibited the JAK2/STAT3 signaling pathway. Conclusions: LINC00893 suppresses the progression of prostate cancer through miR-3173-5p/SOCS3/JAK2/STAT3 pathway. our data uncovers a novel mechanism by which LINC00893 hinders the progression of PCa, which enriches the molecular network of LINC00893 regulating the PCa progression and laies a theoretical foundation for PCa targeted therapy.

The association between occupational asbestos exposure with the risk of incidence and mortality from prostate cancer: a systematic review and meta-analysis

Article

Aug 2021

There is conflicting evidence on the association between asbestos exposure and prostate cancer (PCa). Two recent meta-analyses have claimed that exposure is associated with increased PCa incidence and mortality, but they suffer from some methodological flaws. Given the potential importance of this research question, we aimed to perform a methodologically sound systematic review and meta-analysis to investigate the association between occupational asbestos exposure and the incidence of and mortality from PCa. We followed PRISMA guidelines to systematically search for pertinent articles in three relevant electronic databases: Pubmed, Scopus, and Embase, from their inception to July 2020. The methodological quality of included articles was evaluated using the US National Institutes of Health tool. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) for PCa, as well as respective 95% confidence intervals (CIs), were extracted or calculated for each included cohort. Main and subgroup meta-analyses according to first year of employment, industry, asbestos type, and geographic region were performed. Sixty-five articles comprising 68 cohorts were included. PCa incidence and mortality were not significantly associated with occupational asbestos exposure (pooled SIR: 1.06, 95% CI: 1.00–1.13, P = 0.062; pooled SMR: 1.03, 95% CI: 0.99–1.06, P = 0.115). PCa incidence was higher among workers employed after 1960 (SIR: 1.10, 95% CI: 1.01–1.20). Pooled SIR was elevated in European (SIR: 1.09, 95% CI: 1.01–1.18) and UK cohorts (SIR: 1.05, 95% CI: 1.02–1.09). Mortality was elevated in North American cohorts (SMR: 1.06, 95% CI: 1.02–1.10). Studies of lower methodological quality appeared to yield elevated SIRs or SMRs. This systematic review and meta-analysis provides evidence that men with occupational asbestos exposure have a PCa incidence and mortality similar to that of the general population. Temporal and geographical variables seem to be related to higher SMR or SIR.

Artificial Intelligence Applications in Prostate Cancer Management: Success Stories and Future Ahead

Article

May 2024

This review summarizes and provides an outlook for developments around the use of artificial intelligence (AI) in the diagnosis and treatment of prostate cancer. We searched existing literature on the design and development of new AI-based systems using a non-systematic approach. Areas targeted by AI include the diagnosis, Gleason scoring, biomarker identification, and prognosis of prostate cancer (PCa) from digitised histopathology, segmentation, detection, and classification of PCa from magnetic resonance imaging, AI applications for prostate ultrasound, AI in radiotherapy for PCa including synthetic computed tomography generation and treatment planning and AI in measuring and improving surgical outcomes and education. Recent work has focused on deep learning techniques. Algorithms have achieved results that outperform or are similar to those of experts. However, few proposed algorithms are clinically oriented and can be practically deployed. Future progress needs to be made in data availability, prospective evaluation, regulation, responsible AI, explainability, and practical aspects of clinical deployment.

Current evidence on the relationships among five polymorphisms in the matrix metalloproteinases genes and prostate cancer risk

Article

Full-text available

May 2024

Matrix metalloproteinases (MMPs) had a variety of subtypes, which may be related to tumor invasion and angiogenesis, and the polymorphisms from MMPs have been also associated with the susceptibility to a variety of tumors, including prostate cancer (PCa). However, previous studies have not systematically analyzed the association between MMP and prostate cancer, so we conducted systematic data collection and analyzed to evaluate the relationship among polymorphisms in MMPs and PCa susceptibility. We searched PubMed, Web of Science, Embase and Google Scholar for all papers published up to Apr 3rd, 2023, and systematically analyzed the relationship among MMP1-1607 2G/1G, MMP2-1306 T/C, MMP2-735 T/C, MMP7-181 G/A, MMP9-1562 T/C and PCa susceptibility using multiple comparative models and subgroup analyses. We found that MMP2-1306 T/C polymorphism showed associations with PCa susceptibility, with the Ethnicity subgroup (Asian) being more pronounced. Similarly, MMP9-1562 T/C has also had associations with PCa susceptibility. Our current study found that the polymorphisms of, MMP2-1306 T/C, and MMP9-1562 T/C had strong associations with PCa risk.

The emerging role of non-coding RNAs in the Wnt/β-catenin signaling pathway in Prostate Cancer

Article

Feb 2024
Pathol Res Pract

Prediction of Prostate Cancer Risk Stratifications Based on A Non-Linear Transformation Stacking Learning Strategy

Preprint

Full-text available

Aug 2023

Prostate cancer (PCa) is an epithelial malignancy that occurs in the prostate gland and is generally classified into three risk categories: low, intermediate, and high risk. The most important diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values, but this method can produce false positives leading to unnecessary biopsies, increasing the likelihood of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method to predict PCa risk stratifications. Most current studies on predictions of PCa risk stratification based on clinical data generally perform only a dichotomy of low to intermediate and high risk. This paper proposed a novel machine learning (ML) approach based on a Stacking learning strategy to predict tripartite risk stratifications of PCa. Clinical records with features selected by Lasso were learned by five ML classifiers. Outputs of five classifiers were transformed by various nonlinear transformers (NT) and then, concatenated with the Lasso-selected features to obtain a set of new features. A Stacking learning strategy integrating different ML classifiers was developed based on these new features. Our proposed approach achieved superior performance with an accuracy (ACC) of 0.83 and an Area Under the Receiver Operating Characteristic curve (AUC) value of 0.88 in a dataset of 197 PCa patients with 42 clinical characteristics. This study will better assist clinicians in rapidly assessing PCa risk stratifications while reducing patient burden through AI-related technologies in auxiliary diagnosis of PCa.

Associations of the Geriatric Nutritional Risk Index with High Risk of Prostate Cancer: A cross-sectional study

Article

Jul 2023
NUTRITION

Objectives: The geriatric Nutritional Risk Index (GNRI) is an effective tool to assess the nutritional status of the elderly. However, the relationship between the GNRI and the risk for prostate cancer (PCa) remains uncertain in middle-aged and older men. The aim of this study was to investigate the association between the GNRI and the risk for PCa by analyzing the serum total (tPSA) and free prostate-specific antigen (fPSA) levels (including percent fPSA [%fPSA]). Methods: Data for this study were obtained from 7396 men ≥40 y of age from the 2001-2010 National Health and Nutrition Survey (NHANES). We obtained the tPSA and fPSA and calculated the %fPSA and the GNRI. Participants with %fPSA >25% and tPSA <4 ng/mL were defined as high PCa risk. The relationship between the GNRI and serum PSA levels was investigated using a linear regression model. The odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the GNRI and PCa risk were estimated by a logistic regression model. The non-linear relationship was also characterized by a restricted cubic spline regression model. Results: The median of tPSA, fPSA, and %fPSA was 0.90, 0.26, and 29%, respectively. The mean of the GNRI was 29. The proportion of participants in the low PCa- and high PCa-risk groups was 93% and 7%, respectively. There was a negative and linear correlation between the GNRI and serum tPSA and fPSA levels in all models. However, no association between the GNRI and the %fPSA was observed. In the adjusted model, lower GNRI was associated with higher PCa risk (OR, 0.570; 95% CI, 0.415-0.784; Ptrend = 0.001). The restricted cubic spline regression model showed a non-linear and negative association between the GNRI and PCa risk (Pnon-linearity = 0.020), with inflection points of 109.148. Conclusion: The results of this study suggest that nutritional status, as represented by the GNRI, is associated with the risk for PCa.

RECENT ADVANCES IN THE MEDICAL MANAGEMENT OF PROSTATE CANCER

Article

Mar 1996

RS Kirby

Prostate cancer is a 20th century seedling which, because of its attendant morbidity and mortality and the increased longevity of the population, is set to germinate into a substantial economic burden in the next millennium. Most patients with prostatic cancer present with either locally advanced or metastatic disease, for which palliative endocrine therapies are the first‐line treatment. The increasingly sophisticated and selective hormonal methods available today, such as the longer‐acting formulations of luteinizing hormone‐releasing hormone (LH‐RH) analogues and newer, better‐tolerated, once‐daily, non‐steroidal anti‐androgens, have increased the therapeutic options and improved patient quality of life. Maximum androgen blockade, combining medical or surgical castration with an anti‐androgen, is an increasingly accepted therapy, and offers the greatest efficacy, particularly for patients with a lesser disease burden. The development of hormone‐refractory tumours is still a problem in advanced prostate cancer, although elucidation of the mechanisms involved should offer many potentially fruitful avenues for new therapies.

Phytochemicals in prostate cancer

Chapter

Jan 2023

Factors associated with prostate cancer screening among Indo-Guyanese men

Article

Dec 2022
J NATL MED ASSOC

Introduction: Health screening is considered a vital intervention in public health practices. Despite the strong emphasis on the need for preventative health screenings, little attention is focused on many immigrant populations. Indo-Guyanese immigrants are one of the ethnically minoritized populations facing these challenges. This study aims to identify factors associated with the likelihood that Indo-Guyanese men will undergo screening for prostate cancer. Methods: This study is guided by a mixed-method approach incorporating both quantitative and qualitative analyses. A total of 20 participants were recruited via a snowball technique. Correlation between variables was conducted using IBM SPSS Statistics Version 27, while the qualitative data underwent a rigorous process of analysis and interpretation. Results: Education, income, understanding of risk factors, and considering self at risk were positively correlated with screening. Knowledge of prostate cancer and knowledge of the screening process was negatively correlated with screening. Conclusion: Immigrant health has a significant impact on the U.S. public health system. Timely identification of potential barriers and providing culturally competent solutions and services will ensure a safe and healthy nation.

Evidence of High-Risk Human Papillomavirus in Prostate cancer: A UK based study

Preprint

Full-text available

Jun 2022

Human papillomavirus (HPV) infection is one of the sexually transmitted diseases (STDs) which have been implicated in the etiology of multiple cancers. To date, several studies have been conducted to evaluate the incidence of High-Risk (HR) HPV in prostate cancer (PCa) which have generated widely conflicting data. Hence, this leaves a lack of awareness on the causal role of persistent HPV infection in the development of PCa. Although this has been investigated in a handful of countries, to the best of our knowledge, no prior studies have been conducted in the UK. In this study, polymerase chain reaction (PCR) and Sanger sequencing were implemented to analyze a total of 49 fresh prostate specimens (35 benign and 14 malignant specimens) for the presence of viral DNA of 12 HR-HPV types. Data obtained confirmed the presence of HR-HPV in 32.7% of analyzed benign and malignant prostate tissues with HPV 35 being identified as the most frequent type. Moreover, using Immunohistochemistry (IHC), we have confirmed the expression of HPV protein in prostate tissues positive for HPV DNA. This observation, the first in the UK, suggests that HPV may have a possible etiological role in prostate cancer development.

Myeloid-Derived Suppressor Cells as Key Players and Promising Therapy Targets in Prostate Cancer

Article

Full-text available

Jul 2022

Prostate cancer (PC) is the second most often diagnosed malignancy in men and one of the major causes of cancer death worldwide. Despite genetic predispositions, environmental factors, including a high-fat diet, obesity, a sedentary lifestyle, infections of the prostate, and exposure to chemicals or ionizing radiation, play a crucial role in PC development. Moreover, due to a lack of, or insufficient T-cell infiltration and its immunosuppressive microenvironment, PC is frequently classified as a “cold” tumor. This is related to the absence of tumor-associated antigens, the lack of T-cell activation and their homing into the tumor bed, and the presence of immunological cells with regulatory functions, including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Treg), and tumor-associated macrophages (TAMs). All of them, by a variety of means, hamper anti-tumor immune response in the tumor microenvironment (TME), stimulating tumor growth and the formation of metastases. Therefore, they emerge as potential anti-cancer therapy targets. This article is focused on the function and role of MDSCs in the initiation and progression of PC. Clinical trials directly targeting this cell population or affecting its biological functions, thus limiting its pro-tumorigenic activity, are also presented.

As dificuldades no rastreio e diagnóstico do câncer de próstata: uma revisão integrativa

Article

Full-text available

Jun 2022

No Brasil, o Câncer de Próstata (CaP) é o segundo mais comum em homens e com alta taxa de morbimortalidade. Por isso, preconiza-se a importância do rastreamento precoce a partir dos 50 anos de idade. Assim, este trabalho tem o objetivo de analisar as dificuldades de rastreio e diagnóstico encontradas na Atenção Primária à Saúde (APS) para prevenção do CaP. Trata-se de um estudo de revisão integrativa da literatura, com busca realizada mutuamente por dois pesquisadores na Biblioteca Virtual em Saúde (BVS), Scielo e PubMed, por meio do cruzamento dos descritores “câncer de próstata”, “rastreamento” e “diagnóstico”, com o operador booleano and. Para a realização da busca e seleção dos artigos, foram utilizados os seguintes critérios de elegibilidade: produções dos últimos dois anos; com texto completo disponível; e nos idiomas português, inglês e espanhol. A busca inicial resultou em 488 artigos, dos quais 105 atenderam aos critérios de elegibilidade adotados. Destes, excluídas as duplicidades, sete foram selecionados para comporem o corpus da revisão por atenderem ao objetivo do estudo. Foi possível identificar fatores que dificultam a tomada de decisão dos homens para a realização do rastreio e diagnóstico do CaP, destacando-se crenças, autovulnerabilidade do sexo masculino e a comunicação médica. Além disso, constataram-se divergências entre profissionais de saúde sobre a padronização de critérios para o rastreio. Ressalta-se a necessidade da constância de pesquisas a fim de identificar as dificuldades de rastreio e diagnóstico do CaP.

Support Vector Machines and Naïve Bayes Classifier for Classifying a Prostate Cancer

Chapter

Feb 2022

Prostate Cancer is one of the common types of cancer experienced by men. According to various medical studies, there is a current global increase in the number of men diagnosed with this disease. Therefore, machine learning technology is needed to assist the medical industry in solving this problem. This research, therefore, aims to compare the working accuracy of the Support Vector Machines and Naïve Bayes Classifier. Data were obtained from the dataset of CT scans from Cipto Mangunkusumo Hospital, Indonesia, for its evaluation. The result showed that Support Vector Machines has a better performance than the Naïve Bayes Classifier with an accuracy performance of 83.33% and data training of 90%.

Carriage of mutations R462Q (rs 486907) and D541E (rs 627928) of the RNASEL gene and risk factors in patients with prostate cancer in Burkina Faso.

Preprint

Full-text available

Nov 2021

Background Prostate cancer (Pca) is a public health problem that affects men, usually of middle age or older. It is the second most common cancer diagnosed in men and the fifth leading cause of death. The RNASEL gene located in 1q25 and identified as a susceptibility gene to hereditary prostate cancer, has never been studied in relation to prostate cancer in Burkina Faso. The aim of this study was to analyze the carriage of RNASEL R462Q and D541E mutations and risks factors in patients with prostate cancer in the Burkina Faso. Methods This case-control study included of 38 histologically diagnosed prostate cancer cases and 53 controls (cases without prostate abnormalities). Real-time PCR genotyping of R462Q and D541E variants using the TaqMan® allelic discrimination technique was used. Correlations between different genotypes and combined genotypes were investigated. Results The R462Q variant was present in 5.3% of cases and 7.5% of controls. The D541E variant was present in 50.0% of cases and 35% of controls. There is no association between R462Q variants (OR= 0.60; 95%IC, 0.10 - 3.51; p= 0.686) and D541E variants (OR=2.46; 95%IC, 0.78 - 7.80; p= 0.121) and genotypes combined with prostate cancer. However, there is a statistically significant difference in the distribution of cases according to the PSA rate at diagnosis (p ˂ 0.001). For the Gleason score distribution, only 13.2% of cases have a Gleason score greater than 7. There is a statistically significant difference in the Gleason score distribution of cases (p ˂ 0.001) Conclusions These variants, considered in isolation or in combination, are not associated with the risk of prostate cancer.

Risk Factors for Prostate Cancer

Abstract

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