Abstract
Abstract
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 (∆ß +/− 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.
Funder
Canadian Institutes of Health Research
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference48 articles.
1. Society CC. Prostate cancer statistics - Canadian Cancer Society. Published 2020. http://www.cancer.ca/en/cancer-information/cancer-type/prostate/statistics/?region=qc. Accessed 1 Apr 2020.
2. Research AIfC. Prostate cancer statistics. Published 2018. https://www.wcrf.org/dietandcancer/cancer-trends/prostate-cancer-statisics. Updated 2018-08-22. Accessed 1 Apr 2020.
3. Gandhi J, Afridi A, Vatsia S, et al. The molecular biology of prostate cancer: current understanding and clinical implications. Prostate Cancer Prostatic Dis. 2018;21(1):22–36.
4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2018;67(1):7–30.
5. Litwin MS, Tan HJ. The diagnosis and treatment of prostate Cancer: a review. JAMA. 2017;317(24):2532–42.
Cited by
8 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献