Promoter hypermethylation of Y-chromosome gene PRKY as a potential biomarker for the early diagnosis of prostate cancer

Aim: To develop a methylation marker of Y-chromosome gene in the early diagnosis of prostate cancer (PCa). Materials & methods: We utilized bioinformatics analysis to identify the expression and promoter methylation of Y-chromosome gene PRKY in PCa and other common malignancies. Single-center experiments were conducted to validate the diagnostic value of PRKY promoter methylation in PCa. Results: PRKY expression was significantly down-regulated in PCa and its mechanism may be related to promoter methylation. PRKY promoter methylation is highly specific for the diagnosis of early PCa, which may be superior to prostate-specific antigen, mpMRI and other excellent molecular biomarkers. Conclusion: PRKY promoter methylation may be a potential marker for the early and accurate diagnosis of PCa. Developing excellent diagnostic methylation markers for #prostate cancer! Bioinformatics analysis and experimental verification revealing promoter methylation of Y-chromosome gene PRKY is helpful to identify early prostate cancer, which may be superior to other molecular biomarkers. Y-chromosome gene deletion and down-regulation may promote prostate cancer (PCa) progression. Based on various databases, we finally screened out the Y-chromosome gene PRKY. PRKY expression was significantly down-regulated in PCa tissues and its mechanism may be related to the hypermethylation of promoter region CpG sites (cg05163709, cg08045599 and cg05618150). There was no significant increase of promoter methylation level of PRKY in other common male malignancies (LUAD, LUSC, LIHC, COAD, READ, ESCA, BLCA and pancreatic adenocarcinoma), which indicates that PRKY promoter methylation is highly specific in PCa. PRKY promoter methylation can be detected in very early stages of PCa (T1 & T2, N0, M0, PSA PRKY promoter methylation is a better indicator for the diagnosis of PCa than gene expression (PSA, AMACR and PCA3) and other methylation markers (GSTP1, APC and RARB). The preliminary single-center validation showed that the methylation of cg05163709 and cg05618150 is a promising biomarker, which was significantly better than tPSA and PI-RADS.