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Introduction
Proteins are responsible for all cellular behaviors and activities and also play a key role in disease progression. Proteomics can be an effective tool for identifying diagnostic and therapeutic biomarkers for lung cancer. Cytokines are proteins that play a decisive role in activating the body’s immune system in lung cancer. They can i...
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Context 1
... inflammatory cytokines identified to be a potential target in lung cancer include tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) [79], transforming growth factor-beta (TGF-β) [80], vascular endothelial growth factor (VEGF) [81] and several interleukins such as IL-6, IL-17, IL-8, IL-10, IL-22, IL-1β and IL-18 [82][83][84][85][86][87][88]. The properties of cytokines are summarized in Table 1. ...Context 2
... paper was not funded. Transducer and Activator of Transcription KRAS Kirsten rat sarcoma 2 viral oncogene homolog SP-1 Specificity Protein 1 EMT Epithelial-mesenchymal transition TGFβR1 TGF beta receptor 1 SMAD Sterile Alpha Motif Domain Containing TRAF6 TNF Receptor Associated Factor 6 TAK1 ...Citations
... However, tumor heterogeneity and the high cost of detection may limit the clinical application of this technology (8). Peripheral blood cytokines and immune cells are considered intriguing targets for immunotherapy and clinical biomarker research, as they can reflect changes in the tumor microenvironment during treatment, patient treatment responsiveness, and provide crucial information about the progression of LCA disease (8)(9)(10)(11). Compared to the tumor tissue obtained through surgery, which can only undergo immunoscore testing once (12), peripheral blood samples can be collected throughout the entire treatment of LCA patients, enabling dynamic monitoring of peripheral blood cytokines and immune cells (13,14). ...
Objective
Cytokines and cell subsets are important components of the tumor microenvironment. Previous research has revealed that there are differences in cytokines and cell subsets in the peripheral blood of lung cancer (LCA) patients before and after eradication. The purpose of this study is to explore the monitoring value of cytokines and cellular subpopulations as biomarkers in post-immunotherapy monitoring of patients with LCA after surgery
Methods
We conducted a case-control study using double-antibody sandwich magnetic microsphere flow cytometry with immunofluorescence technology and fluorescent monoclonal antibody multiparameter flow cytometry to detect differences in peripheral blood cytokines and cell subsets between LCA patients after immunotherapy and healthy controls.
Results
Our research results show that there are differences in the levels of IL-4, IL-6, IL-10, IL-17, IFN-γ, TNF-α in the peripheral blood of LCA patients (n=70) after immunotherapy compared to the healthy controls (n=55) (P<0.05), and there are differences in 10 cell subgroups including DP T Cells, AT cells, and NLR in the peripheral blood compared to the healthy controls (n=35) (P<0.05). Further analysis revealed significant differences in the detection data of IL-6, IL-10, IFN-γ, CD56dim NK cells, Total B cells, Total NE cells, CD15⁺M cells, and NLR between LCA deceased patients (n=25) and LCA surviving patients (n=27) during the same period (P<0.05). The continuous monitoring of cytokines and cell subsets is far more valuable than a single-time test, as abnormal fluctuations in the data of cytokines and cell subsets are often associated with poor prognosis. In addition, IL-6 and NLR showed the strongest discriminative ability between postoperative immunotherapy-treated LCA patients and healthy controls, with AUC values of 0.840 and 0.822, respectively. There was a significant association between IFN-γ and distant metastasis in LCA (P<0.05), as well as between CD56dim NK cells and lymph node infiltration (P<0.05).
Conclusion
This research results support peripheral blood cytokines and cell subsets as biomarkers for monitoring the postoperative immune status and predicting the prognosis of LCA patients after immunotherapy. The continuous monitoring of cytokines and cell subsets is far more valuable than a single-time detection.
... In the study by Travier et al. (2007), it was found that an increase in HbA1c levels poses a risk for respiratory cancers. Cytokines are small proteins that play important roles in cancer development (Abolfathi et al., 2021). IL6, a pleiotropic cytokine, functions in the regulation of the immune system (Yao et al., 2014). ...
Background/aim: The complicated nature of tumor formation makes it difficult to identify discriminatory genes. Recently, transcriptome-based supervised classification methods using support vector machines (SVMs) have become popular in this field. However, the inclusion of less significant variables in the construction of classification models can lead to misclassification. To improve model performance, feature selection methods such as enrichment analysis can be used to extract useful variable sets. The detection of genes that can discriminate between normal and tumor samples in the association of cancer and disease remains an area of limited information. We therefore aimed to discover novel and practical sets of discriminatory biomarkers by utilizing the association of cancer and disease.
Materials and methods: In this study, we employed an SVM classification method for differentially expressed genes enriched by Disease Ontology and filtered nondiscriminatory features using Wilk’s lambda criterion prior to classification. Our approach uses the discovery of disease-associated genes as a viable strategy to identify gene sets that discriminate between tumor and normal states. We analyzed the performance of our algorithm using comprehensive RNA-Seq data for adenocarcinoma of the colon, squamous cell carcinoma of the lung, and adenocarcinoma of the lung. The classification performance of the obtained gene sets was analyzed by comparison with different expression datasets and previous studies using the same datasets.
Results: It was found that our algorithm extracts stable small gene sets that provide high accuracy in predicting cancer status. In addition, the gene sets generated by our method perform well in survival analyses, indicating their potential for prognosis.
Conclusion: By combining gene sets for both diagnosis and prognosis, our method can improve clinical applications in cancer research. Our algorithm is available as an R package with a graphical user interface in Bioconductor (https://doi.org/10.18129/B9.bioc.SVMDO) and GitHub (https://github.com/robogeno/SVMDO).
... Обнаруженные сдвиги свидетельствуют о том, что в организме больных НМРЛ происходят активные процессы, связанные с ростом злокачественных клеток, воспалением, угнетением гуморального иммунитета и тканевой гипоксией. Все они вполне укладываются в рамки современных представлений о характере изменений со стороны иммунной системы и продукции ЭКСПЕРИМЕНТАЛЬНАЯ СТАТЬЯ | EXPERIMENTAL REPORT проангиогенных факторов при злокачественных новообразованиях [15,16]. С целью углубления существующих представлений о механизмах формирования подобных изменений при НМРЛ было изучено содержание в крови больных продуктов катаболизма триптофана Pseudomonas aeruginosa HHQ и PQS. ...
Introduction . Researchers in the field of oncology have a significant interest in the role of microorganisms in development of malignant neoplasms.
Aim . To study the levels of 2-heptyl-3-hydroxy-4-quinolone (PQS) and 2-heptyl-4-quinolone (HHQ) produced by Pseudomonas aeruginosa in the blood of patients with lung cancer and to analyze the relation between their changes and changes in the level of immunoglobulins and vascular endothelial growth factor (VEGF) in the blood of patients with lung cancer.
Materials and methods . PQS and HHQ were quantified in the blood of patients using high performance liquid chromatography. The levels of immunoglobulins G (IgG), secretory immunoglobulin A (s-IgA), and VEGF in the blood were determined using ELISA.
Results . Analysis have shown that the level of PQS in the blood of patients with lung cancer is 2-fold higher than in the control group. This change is accompanied by a decrease in the level of immunoglobulins IgG, as well as an increase in the content of s-IgA and growth factor VEGF in the blood.
Conclusion . PQS level in the blood of patients with lung cancer is elevated creating conditions aggravating the course of the main disease and worsening its prognosis.
... Proteomics-based analysis plays a fundamental role in tumor diagnostics and therapeutics by discovering potential biomarkers to detect early stages of cancer and inhibit carcinogenesis [47,48]. The scarcity of precision and personalized medicine in anti-cancer therapy contributes to conjure resistance and survival [49]. ...
... Markers of therapeutical use include Vascular Endothelial Growth Factor (VEGF) coupled with angiogenesis; Tumor Necrosis Factor (TNF)-alpha associated with tumor suppression; Epidermal Growth Factor Receptor (EGFR); and Transforming Growth Factor (TGF)-beta expressions linked with either tumor survival or apoptosis. Specific targeted approaches along with other pharmacological limitations could be realistically implemented in LUAD clinical research practice with the advancements of proteomics [47]. Xu et al. carried out a comprehensive proteomics analysis of 103 cases of LUAD, the most common of non-small-cell lung cancers and most common subtype in non-smokers [67]. ...
... This is largely due to lack of known genetic alterations in the key oncogenic signaling pathways and the difficulty of targeting oncogenic mutations (KRAS mutations) [67,76,77]. Additionally, a lack of early detection and diagnosis markers contributes towards this disease [47]. The proteome-based stratification of LUAD will lay a foundation for understating the heterogeneous nature of the disease and for developing new therapeutic approaches. ...
Recent advances in the field of proteomics have allowed extensive insights into the molecular regulations of the cell proteome. Specifically, this allows researchers to dissect a multitude of signaling arrays while targeting for the discovery of novel protein signatures. These approaches based on data mining are becoming increasingly powerful for identifying both potential disease mechanisms as well as indicators for disease progression and overall survival predictive and prognostic molecular markers for cancer. Furthermore, mass spectrometry (MS) integrations satisfy the ongoing demand for in-depth biomarker validation. For the purpose of this review, we will highlight the current developments based on MS sensitivity, to place quantitative proteomics into clinical settings and provide a perspective to integrate proteomics data for future applications in cancer precision medicine. We will also discuss malignancies associated with oncogenic viruses such as Acquire Immunodeficiency Syndrome (AIDS) and suggest novel mechanisms behind this phenomenon. Human Immunodeficiency Virus type-1 (HIV-1) proteins are known to be oncogenic per se, to induce oxidative and endoplasmic reticulum stresses, and to be released from the infected or expressing cells. HIV-1 proteins can act alone or in collaboration with other known oncoproteins, which cause the bulk of malignancies in people living with HIV-1 on ART.
... The majority of lung cancer patients are diagnosed at a late stage, which contributes to a poor prognosis for their long-term survival. This is because there are not enough clinical tests that are noninvasive that can be used for early diagnosis and screening of these individuals [5,6]. Due to this, it is essential to locate certain biomarkers in order to arrive at an accurate diagnosis as quickly as feasible [5]. ...
... This is because there are not enough clinical tests that are noninvasive that can be used for early diagnosis and screening of these individuals [5,6]. Due to this, it is essential to locate certain biomarkers in order to arrive at an accurate diagnosis as quickly as feasible [5]. ...
... The innate immune response and the acquired immune response both serve to illustrate the functional connection that exists between inflammation and cancer. Inflammatory cells and tumor cells both release cytokines and chemokines, which are proteins that have a function in increasing activity in both cells and the humoral system [5,6,9]. ...
The role of chronic inflammation in the initiation and progression of carcinogenesis has been well-established in previous studies, particularly in the stages of malignant conversion, invasion, and metastasis. This study aimed to explore the potential correlation between the levels of cytokines in serum and bronchoalveolar lavage fluid (BALF) by comparing their levels between patients with lung cancer and those with benign lung diseases. The study measured the concentration of IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, and IL-12p70, in venous blood and BALF of a total of 33 patients with lung cancer and 33 patients with benign lung diseases. Significant differences were found between the two groups in various clinical parameters. The cytokine levels were significantly higher among patients with malignant disease, while the BALF analysis revealed higher cytokine levels compared with serum analysis. It was discovered that the levels of cancer-specific cytokines in the lavage fluid increased significantly sooner and were present at a greater concentration than those in the peripheral blood. After one month of treatment, the serum markers decreased significantly but slower in the lavage fluid. The differences between serum and BALF markers remained significant. It was observed that the highest correlation was among IL-6 (serum) and IL-6 (lavage), with a coefficient of 0.774 (p-value < 0.001), and IL-1 (serum) and IL-1β (lavage), with a coefficient value of 0.610 (p-value < 0.001). Other significant correlations among serum and lavage cytokines were observed between IL-6 (lavage) and IL-1 (serum) (rho = 0.631, p-value < 0.001) and CRP (rho = 0.428, p-value = 0.001), respectively. This study revealed significant differences and correlations in clinical parameters, serum markers, and BALF inflammatory markers between patients with lung cancer and those with benign lung pathologies. The results highlight the importance of understanding the inflammatory profiles of these conditions and could contribute to the development of targeted therapies or diagnostic approaches in the future. Further research is needed to validate these findings, explore their implications for clinical practice, and determine the diagnostic and prognostic value of these cytokines for lung cancer.
... Current research efforts focus on elucidating the role of cytokines in lung cancer and identifying potential biomarkers that can be used for diagnosis, prognosis assessment, and therapy response evaluation [15]. Several studies have demonstrated the potential utility of detecting specific cytokines, such as interleukins, tumor necrosis factors, and tumor growth factors, in bronchoalveolar lavage fluid or blood samples for the differential diagnosis of lung cancer and proliferation of cancer cells [16]. ...
Lung cancer is a leading cause of cancer-related mortality worldwide. Identifying novel diagnostic and prognostic biomarkers is essential for improving patient outcomes. This study aimed to investigate the predictive role of cytokines from bronchoalveolar lavage fluid (BALF) in lung cancer diagnosis and prognosis. A prospective study was conducted on 33 patients with suspected lung cancer, divided into inflammatory and non-inflammatory BALF groups. Inflammatory markers in BALF were assessed, and their association with lung cancer risk was analyzed using receiver operating characteristic (ROC) plot analysis, sensitivity and specificity percentages, and regression analysis. Statistically significant differences were observed between the inflammatory and non-inflammatory groups for several inflammatory markers, including IFN-gamma, IL-1b, IL-2, IL-6, IL-10, and IL-12p70. In the follow-up analysis, significant differences persisted for IFN-gamma, IL-1b, IL-2, IL-4, and IL-6. ROC plot analysis revealed that IL-12p70 had the highest area under the curve (AUC) value (0.702), followed by IL-2 (0.682), IL-6 (0.620), IL-4 (0.611), TNF-alpha (0.609), IL-10 (0.604), IL-1b (0.635), and IFN-gamma (0.521). IL-6 showed the highest sensitivity (73%), and IL-1b had the highest specificity (69%). Regression analysis demonstrated that IL-6 (cut-off = 25 pg/mL) and IL-12p70 (cut-off = 30 pg/mL) had the highest odds ratios for lung cancer risk, at 5.09 (95% CI: 2.38–9.24, p < 0.001) and 4.31 (95% CI: 1.85–8.16, p < 0.001), respectively. Cytokines from BALF, particularly IL-6 and IL-12p70, show potential as diagnostic and prognostic biomarkers for lung cancer. Further studies with larger cohorts are warranted to confirm these findings and elucidate the clinical implications of these markers in lung cancer management.
... Lung cancer is cancer that most often begins in the lungs but is sometimes the result of Cancer spreading from adjacent areas. Lung cancer is divided into two groups non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) [1,2]. Risk factors for lung cancer include two groups of genetic and environmental factors, environmental factors such as smoking, asbestos exposure, radon gas, air pollution, and age [3][4][5][6]. ...
... Lung cancer is the deadliest of all cancers [1,2]. High resistance to chemotherapy and aggression has increased the need for reliable prognostic assay and effective treatments for the disease. ...
Background
Lung cancer is one of the leading causes of death in the world and the deadliest of all cancers. Apoptosis is a key pathway in regulating the cell growth rate, proliferation, and occurrence of lung cancer. This process is controlled by many molecules, such as microRNAs and their target genes. Therefore, finding new medical approaches such as exploring diagnostic and prognostic biomarkers involved in apoptosis is needed for this disease. In the present study, we aimed to identify key microRNAs and their target genes that could be used in the prognosis and diagnosis of lung cancer.
Methods
Signaling pathways, genes, and microRNAs involved in the apoptotic pathway were identified by bioinformatics analysis and recent clinical studies. Bioinformatics analysis was performed on databases including NCBI, TargetScan, UALCAN, UCSC, KEGG, miRPathDB, and Enrichr, and clinical studies were extracted from PubMed, web of science, and SCOPUS databases.
Results
NF-κB, PI3K/AKT, and MAPK pathways play critical roles in the regulation of apoptosis. MiR-146b, 146a, 21, 23a, 135a, 30a, 202, and 181 were identified as the involved microRNAs in the apoptosis signaling pathway, and IRAK1, TRAF6, Bcl-2, PTEN, Akt, PIK3, KRAS, and MAPK1 were classified as the target genes of the mentioned microRNAs respectively. The essential roles of these signaling pathways and miRNAs/target genes were approved through both databases and clinical studies. Moreover, surviving, living, BRUCE, and XIAP was the main inhibitor of apoptosis which act by regulating the apoptosis-involved genes and miRNAs.
Conclusion
Identifying the abnormal expression and regulation of miRNAs and signaling pathways in apoptosis of lung cancer can represent a novel class of biomarkers that can facilitate the early diagnosis, personalized treatment, and prediction of drug response for lung cancer patients. Therefore, studying the mechanisms of apoptosis including signaling pathways, miRNAs/target genes, and the inhibitors of apoptosis are advantageous for finding the most practical approach and reducing the pathological demonstrations of lung cancer.
... IL-6 is associated with the production of lung cancer cells, postoperative recovery, quality of survival, and disease malignancy, and it inhibits the antitumor immune response ability of normal human cells, contributing to further development of lung cancer. IL-10 promotes the phagocytosis of mononuclear macrophages, Evidence-Based Complementary and Alternative Medicine the expression of various receptors [15], and the activation and proliferation of CD8+ T cells, thereby enhancing the body's antitumor capacity and inhibiting the secretion of proinflammatory cytokines. TNF-α mediates the body's autoimmune response, but its persistent release may aggravate the body's pathological damage and promote tumor proliferation. ...
Purpose:
To investigate the clinical value of interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) in diagnosis and severity assessment of lung cancer.
Methods:
In this observational study, 50 physical examination healthy subjects were included in the control group and 100 lung cancer patients were included in the study group. In the study group, 53 cases with pleural effusion were subgrouped to the pleural effusion group (n = 53), while 47 patients were assigned to the nonpleural effusion group (n = 47). Plasma cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of all eligible subjects were collected and compared.
Results:
The study group showed significantly higher levels of plasma cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ versus healthy subjects (P < 0.05). Deterioration of lung cancer was associated with increased plasma cytokine levels and APACHE II scores. The combination assay of the above plasma cytokines showed significantly better diagnostic efficacy for lung cancer versus the single assay of the cytokines. Dead patients had higher plasma cytokine levels versus survived patients. The accuracy of plasma IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ levels in the severity assessment of lung cancer was comparable with that of the APACHE II scale.
Conclusion:
The plasma cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ are effective markers for the diagnosis of lung cancer. The combined assay contributes to the early diagnosis of lung cancer patients, and the persistent elevation of cytokines suggests an increased risk of death in lung cancer patients, so the detection of cytokine levels facilitates the severity assessment of lung cancer.
... Lung cancer is the leading cause of death worldwide, with high incidence rate and mortality [1][2][3][4][5]. Nonsmall cell lung cancer (NSCLC) refers to all epithelial cell lung cancer except small cell lung cancer. ...
Nonsmall cell lung cancer (NSCLC) is a serious threat to the life and health of patients with high incidence rate and mortality. The present research was to assess the relationship between the serum Krüppel-like factor 7 (KLF7) level and the recurrence and metastasis of NSCLC patients. 150 patients with NSCLC treated by thoracoscopic radical resection of lung cancer in our hospital from January 2016 to February 2017 were selected. As the control group, 148 healthy people who went to the hospital for physical examination in the same period were screened. The expression levels of serum KLF7 in the observation group and the control group were compared and analyzed. According to the level of KLF7 expression, the patients in the observation group were divided into KLF7 high expression group (≥258.6 ng/L, n =75) and KLF7 low expression group (<258.6 ng/L, n =75). The 3-year recurrence and metastasis rate of patients in each group was compared and analyzed. It was found the concentration of serum KLF7 in peripheral blood of NSCLC (2.25 ± 0.65) ng/ml was significantly higher than that in healthy population (1.42 ± 0.38) ng/ml ( P < 0.05 ). The expression level of serum KLF7 was not related to gender, age, smoking history, and tumor diameter of NSCLC patients ( P > 0.05 ), but related to the degree of differentiation and TNM stage of NSCLC patients ( P < 0.05 ). Univariate analysis showed that the degree of differentiation, TNM stage, and KLF7 were significantly correlated with 3-year recurrence and metastasis of NSCLC patients ( P < 0.05 ). Cox regression analysis showed that low degree of differentiation, TNM stage IIIa, and KLF7 were independent risk factors for recurrence and metastasis in NSCLC patients in 3 years ( P < 0.05 ). Taken together, the expression level of serum KLF7 in patients with NSCLC is significantly increased, which is an independent risk factor for recurrence and metastasis in 3 years, and is worthy of clinical application.
... For those who have advanced LUAD, the prognosis remains poor. Patients with LUAD have a 50% lower chance of surviving if they develop metastasis or recurrence, which is the primary cause of the poor prognosis [36,37]. Nonspecific symptoms of LUAD make it difficult to diagnose the disease, which delays treatment. ...
Lung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. More and more studies have reported that mitochondrial-related genes (MTRGs) were associated with the clinical outcomes of multiple tumors solely. In this study, we aimed to develop a novel prognostic model based on MTRGs. Differentially expressed MTRGs were identified from TCGA-LUAD and GSE31210 cohorts. Univariate Cox regression analysis was utilized to screen differentially expressed MTRGs that were related to prognosis of LUAD. Then, LASSO Cox regression analysis was used to develop a prognostic signature. ESTIMATE was used for estimating the fractions of immune cell types. In this study, we identified 44 overlapping differentially expressed MTRGs in TCGA-LUAD and GSE31210 cohorts. Among 44 overlapping differentially expressed MTRGs, nine genes were associated with prognosis of LUAD. When the penalty parameter lambda was the minimum, there were six genes meeting the conditions of constructing the signature, including SERPINB5, CCNB1, FGR MAOB, SH3BP5, and CYP24A1. The survival analysis suggested that prognosis of patients in the high-risk group was significantly worse than that in the low-risk group. Cox regression analyses showed that the risk score was an independent predictor of LUAD prognosis. As with the results of ESTIMATE score, the degree of immune cell infiltration in the low-risk group was higher than that in the high-risk group, such as TIL, Treg, and B cells. In addition, TMB and cancer stem cell infiltration were higher in the low-risk group than the high-risk group. In conclusion, we developed a novel MTRG signature acting as a negative independent prognostic factor. In the future, individualized treatments and medical decision-making may benefit from using the predicted model.
