Correlating blood-based DNA methylation markers and prostate cancer risk in African-American men

Moses-Fynn, Emmanuel; Tang, Wei; Beyene, Desta; Apprey, Victor; Copeland, Robert L.; Kanaan, Yasmine; Kwabi-Addo, Bernard

doi:10.1371/journal.pone.0203322

Cited by 12 publications

(14 citation statements)

References 49 publications

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“…We found that the SPARC gene promoter region was not methylated in the GES-1 cell line but found that the other four GC cell lines showed methylation. Similar conclusions were previously reported for pancreatic cancer[22], prostate cancer[23], and colon cancer[24]. These results also revealed that the methylation frequency of SPARC was positively associated with TNM stage, macroscopic type, and lymph node metastasis.…”

Section: Discussionsupporting

confidence: 90%

Aberrant methylation of secreted protein acidic and rich in cysteine gene and its significance in gastric cancer

Shao

Zhou

Dai

2019

WJG

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BACKGROUNDAberrant methylation in DNA regulatory regions could downregulate tumor suppressor genes without changing the sequences. However, our knowledge of secreted protein acidic and rich in cysteine (SPARC) and its aberrant methylation in gastric cancer (GC) is still inadequate. In the present research, we performed fundamental research to clarify the precise function of methylation on SPARC and its significance in GC.AIMTo investigate promoter methylation and the effects of the SPARC gene in GC cells and tissues and to evaluate its clinical significance.METHODSPlasmids that overexpressed the SPARC gene were transfected into human GC BGC-823 cells; non-transfected cells were used as a control group (NC group). Quantitative real-time polymerase chain reaction and western blotting (WB) were then used to detect the expression of SPARC. Methylation-specific polymerase chain reaction was executed to analyze the gene promoter methylation status. Cell viability was measured by the cell counting kit-8 assay. The migration and invasion ability of cells were detected by scratch assays and transwell chamber assays, respectively. Cell cycle events and apoptosis were observed with a flow cytometer.RESULTSThe expression of SPARC mRNA in GC tissues and cells was significantly lower and showed differing degrees of hypermethylation, respectively, than that in normal adjacent tissues and control cells. Treatment with 5-Aza-2’-deoxycytidine (5-Aza-Cdr) was able to restore the expression of SPARC and reverse promoter hypermethylation. Overexpression of the SPARC gene significantly inhibited proliferation, migration, and invasion of GC cells, while also causing cell cycle arrest and apoptosis; the NC group exhibited the opposite effects.CONCLUSIONThis study demonstrated that SPARC could function as a tumor suppressor and might be silenced by promoter hypermethylation. Furthermore, in GC cells, SPARC inhibited migration, invasion, and proliferation, caused cell cycle arrest at the G0/G1 phase, and promoted apoptosis.

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Section: Discussionsupporting

confidence: 90%

Aberrant methylation of secreted protein acidic and rich in cysteine gene and its significance in gastric cancer

Shao

Zhou

Dai

2019

WJG

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“…A study investigating clinical significance of gene promoter DNA methylation in blood DNA found six genes promoter methylation of PCa patients to be significantly different from controls [38]. However, we did not see such differences which could be due to several reasons; firstly, T cells DNA was used in our study while blood DNA was used in previous study [38]; secondly, previous study was carried out in African American men while our study had mostly Caucasian men [38]. Also, using whole blood DNA, no association between the DNA methylation on all CG sites and risk of PCa or aggressive disease was observed [39].…”

Section: Discussionmentioning

confidence: 99%

DNA methylation signatures of Prostate Cancer in peripheral T-cells

et al. 2020

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Background: Prostate Cancer (PCa) is the second most common cancer in men where advancements have been made for early detection using imaging techniques, however these are limited by lesion size. Immune surveillance has emerged as an effective approach for early detection and to monitor disease progression. In recent studies, we have shown that host peripheral blood immune cells undergo changes in DNA methylation in liver and breast cancer. Methods: In the current study, we examined the DNA methylation status of peripheral blood T cells of men with positive biopsy for PCa versus men with negative biopsy having benign prostate tissue, defined as controls. T cells DNA was isolated and subjected to Illumina Infinium methylation EPIC array and validated using Illumina amplicon sequencing and pyrosequencing platforms. Results: Differential methylation of 449 CG sites between control and PCa T cell DNA showed a correlation with Gleason score (p < 0.05). Two hundred twenty-three differentially methylated CGs between control and PCa (Δß +/− 10%, p < 0.05), were enriched in pathways involved in immune surveillance system. Three CGs which were found differentially methylated following DMP (Differentially methylated probes) analysis of ChAMP remained significant after BH (Benjamini-Hochberg) correction, of which, 2 CGs were validated. Predictive ability of combination of these 3 CGs (polygenic methylation score, PMS) to detect PCa had high sensitivity, specificity and overall accuracy. PMS also showed strong positive correlation with Gleason score and tumor volume of PCa patients. Conclusions: Results from the current study provide for the first-time a potential role of DNA methylation changes in peripheral T cells in PCa. This non-invasive methodology may allow for early intervention and stratification of patients into different prognostic groups to reduce PCa associated morbidity from repeat invasive prostate biopsies and design therapeutic strategy to reduce PCa associated mortality.

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“…Prostate cancer (PCa) is a complex disease, with risk factors and outcomes influenced by a combination of socioeconomic status, access to care (AtC) and quality of care (QoC) delivery, lifestyle factors, variations in inherited genetics and molecular tumor profiles (biology), as well as epigenetics [1][2][3][4][5]. In the USA, Black men are approximately 80% more likely to be diagnosed with and 220% more likely to die from PCa in comparison to White men [6].…”

Section: Introductionmentioning

confidence: 99%

Prostate Cancer Racial Disparities: A Systematic Review by the Prostate Cancer Foundation Panel

Mahal

Gerke

Awasthi

et al. 2022

European Urology Oncology

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Context: Prostate cancer (PCa) is a complex disease that disproportionately impacts Black men in the USA. The structural factors that drive heterogeneous outcomes for patients of differing backgrounds are probably the same ones that result in population-level disparities. The relative contribution of drivers along the PCa disease continuum is an active area of investigation and debate. Objective: To critically synthesize the available evidence on PCa disparities from a population-level perspective in comparison to data from "equal access and equal care settings" and to provide a consensus summary of the state of PCa disparities. Evidence acquisition: A plenary panel on PCa disparities presented at the Prostate Cancer Foundation meeting on October 24, 2019 and ensuing discussions are reported here. We used a systematic literature review approach and the Preferred Reporting Items for Systematic Reviews and Meta-analyses to select the most relevant publications. A total of 3333 publications between 2011 and 2021 were retrieved, of which 52 were included in the review; an additional 13 articles on screening guidelines, seminal clinical trials, and statistical methodology were used in the evidence synthesis. Evidence synthesis: Race disparities in PCa are a result of a complex interaction between socioeconomic factors impacting access to care and ancestral/genetic factors that may influence tumor biology. Black men in the USA continue to have a nearly 1.8 times higher population-level mortality rate than White men. Failure to account for the race-specific incidence burden would continue to lead to residual y These authors contributed equally and are joint first authors.

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Correlating blood-based DNA methylation markers and prostate cancer risk in African-American men

Cited by 12 publications

References 49 publications

Aberrant methylation of secreted protein acidic and rich in cysteine gene and its significance in gastric cancer

Aberrant methylation of secreted protein acidic and rich in cysteine gene and its significance in gastric cancer

DNA methylation signatures of Prostate Cancer in peripheral T-cells

Prostate Cancer Racial Disparities: A Systematic Review by the Prostate Cancer Foundation Panel

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