Figure - available from: Extracellular Vesicles and Circulating Nucleic Acids
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Illustration of maternal plasma DNA and an example of the fragment size (in bp) distribution of fetal-specific DNA (green) and shared (maternal and fetal; blue) DNA. cffDNA has shifted size distribution, being overall shorter than the maternal counterparts.
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Noninvasive sampling of an individual’s body fluids is an easy means to capture circulating cell-free DNA (cfDNA). These small fragments of DNA carry information on the contributing cell’s genome, epigenome, and nuclease content. Analysis of cfDNA for the assessment of genetic risk has already revolutionized clinical practice, and a compendium of i...
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Metastatic prostate cancer remains a major clinical challenge and metastatic lesions are highly heterogeneous and difficult to biopsy. Liquid biopsy provides opportunities to gain insights into the underlying biology. Here, using the highly sensitive enrichment-based sequencing technology, we provide analysis of 60 and 175 plasma DNA methylomes fro...
Gastric cancer remains a leading cause of cancer-related death worldwide, largely due to inadequate screening methods, late diagnosis, and limited treatment options. Liquid biopsy has emerged as a promising non-invasive approach for cancer screening and prognosis by detecting circulating tumor components like circulating tumor DNA (ctDNA) in the bl...
Citations
... While NETs and consequently neutrophils clearly appear as a significant biological source of cir-nDNA, 26,58 cir-nDNA in COVID-19 patients may also derive from other origins, such as damaged organ tissue. For instance, Y. Dor's team recently reported elevated levels of lungderived cir-nDNA among COVID-19 patients, with such levels being significantly associated with disease severity and mortality. ...
We examined from a large exploratory study cohort of COVID-19 patients (N = 549) a validated panel of neutrophil extracellular traps (NETs) markers in different categories of disease severity. Neutrophil elastase (NE), myeloperoxidase (MPO), and circulating nuclear DNA (cir-nDNA) levels in plasma were seen to gradually and significantly (p < 0.0001) increase with the disease severity: mild (3.7, 48.9, and 15.8 ng/mL, respectively); moderate (9.8, 77.5, and 27.7 ng/mL, respectively); severe (11.7, 99.5, and 29.0 ng/mL, respectively); and critical (13.1, 110.2, and 46.0 ng/mL, respectively); and are also statistically different with healthy individuals (N = 140; p < 0.0001). All observations made in relation to the Delta variant-infected patients are in line with Omicron-infected patients. We unexpectedly observed significantly higher levels of NETs in asymptomatic individuals as compared to healthy subjects (p < 0.0001). Moreover, the balance of cir-nDNA and circulating mitochondrial DNA level was affected in COVID-19 infected patients attesting to mitochondrial dysfunction.
... Therefore, changes in DNA methylation levels have been detected as biomarkers for cancer diagnosis [70]. Currently, multiple DNA methylation sequencing techniques have been developed, including whole genome bisulfite sequencing (WGBS) [71], reduced representation bisulfite sequencing (RRBS) [72], oxidative bisulfite sequencing (oxBS-seq) [73], and cellfree methylated DNA immunoprecipitation and highthroughput sequencing (cfMeDIP-seq) [74]. ...
Abstract Rather than a “short‐term tenant,” the tumor microbiome has been shown to play a vital role as a “permanent resident,” affecting carcinogenesis, cancer development, metastasis, and cancer therapies. As the tumor microbiome has great potential to become a target for the early diagnosis and treatment of cancer, recent research on the relevance of the tumor microbiota has attracted a wide range of attention from various scientific fields, resulting in remarkable progress that benefits from the development of interdisciplinary technologies. However, there are still a great variety of challenges in this emerging area, such as the low biomass of intratumoral bacteria and unculturable character of some microbial species. Due to the complexity of tumor microbiome research (e.g., the heterogeneity of tumor microenvironment), new methods with high spatial and temporal resolution are urgently needed. Among these developing methods, multi‐omics technologies (combinations of genomics, transcriptomics, proteomics, and metabolomics) are powerful approaches that can facilitate the understanding of the tumor microbiome on different levels of the central dogma. Therefore, multi‐omics (especially single‐cell omics) will make enormous impacts on the future studies of the interplay between microbes and tumor microenvironment. In this review, we have systematically summarized the advances in multi‐omics and their existing and potential applications in tumor microbiome research, thus providing an omics toolbox for investigators to reference in the future.
... However, an easily accessible source for genetic information is cell-free DNA (cfDNA), which is ubiquitous in body fluids, such as blood (serum or plasma), urine, cerebrospinal fluid, saliva, sperm and others. cfDNA is mostly derived from apoptotic or necrotic cells originating from hematopoietic cells, stromal cells and endothelial cells, but in cancer patients, it is also derived from primary, relapsed or metastatic tumor cells [9]. In addition, the release of tumor cfDNA by the active secretion of extracellular vesicles has been suggested [10]. ...
In the present study, we further analyzed the data obtained in our previous study, where we investigated the cell-free DNA (cfDNA) of 34 progressive prostate cancer patients via targeted sequencing. Here, we studied the occurrence and prognostic impact of sequence variants according to their clinical pathological significance (CPS) or their functional impact (FI) in 23 DNA damage repair (DDR) genes with a focus on the ATM serine/threonine kinase gene (ATM). All patients had at least one DDR gene with a CPS or FI variant. Kaplan‒Meier analysis indicated that the group with a higher number of CPS variants in DDR genes had a shorter time to treatment change (TTC) compared to the group with a lower number of CPS variants (p = 0.038). Analysis of each DDR gene revealed that CPS variants in the ATM gene and FI variants in the nibrin (NBN) gene showed a shorter TTC (p = 0.034 and p = 0.042). In addition, patients with CPS variants in the ATM gene had shorter overall survival (OS; p = 0.022) and disease-specific survival (DSS; p = 0.010) than patients without these variants. Interestingly, patients with CPS variants in seven DDR genes possessed a better OS (p = 0.008) and DSS (p = 0.009), and patients with FI variants in four DDR genes showed a better OS (p = 0.007) and DSS (p = 0.008). Together, these findings demonstrated that the analysis of cfDNA for gene variants in DDR genes provides prognostic information that may be helpful for future temporal and targeted treatment decisions for advanced PCa patients.
Defining the number and abundance of different cell types in tissues is important for understanding disease mechanisms as well as for diagnostic and prognostic purposes. Typically, this is achieved by immunohistological analyses, cell sorting, or single-cell RNA-sequencing. Alternatively, cell-specific DNA methylome information can be leveraged to deconvolve cell fractions from a bulk DNA mixture. However, comprehensive benchmarking of deconvolution methods and modalities was not yet performed. Here we evaluate 16 deconvolution algorithms, developed either specifically for DNA methylome data or more generically. We assess the performance of these algorithms, and the effect of normalization methods, while modeling variables that impact deconvolution performance, including cell abundance, cell type similarity, reference panel size, method for methylome profiling (array or sequencing), and technical variation. We observe differences in algorithm performance depending on each these variables, emphasizing the need for tailoring deconvolution analyses. The complexity of the reference, marker selection method, number of marker loci and, for sequencing-based assays, sequencing depth have a marked influence on performance. By developing handles to select the optimal analysis configuration, we provide a valuable source of information for studies aiming to deconvolve array- or sequencing-based methylation data.
The purpose of this study was to evaluate and identify the health-seeking behaviors, its associated factors, and the relationship between these factors to the health seeking behavior of young adults in Barangay Quiot Pardo, Cebu City. A sample size 332 respondents participated in the study. All the respondents were able to meet the inclusion criteria. The respondents were given likert-scale questionnaires online. Data were analyzed using SPSS. The findings of this study show that out of the 332 respondents, only 116 of those have sought treatment for their disease in the past 12 months. From the 332 young adults who participated in this study, the results showed that psychological, individual, and socio-cultural and familial factors have a significant relationship to the individual's decision to seek treatment during the period of disease while situational and marketing factors show no relationship to young adults' overall health-seeking behavior. The researchers conclude that psychological, individual, sociocultural and familial factors influence the health-seeking behaviors among young adults aging 20 to 24 years old residing in Barangay Quiot Pardo, Cebu City. The situational and marketing factors are less likely to affect the respondents' behavior.
