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Results: PRKY expression was significantly down-regulated in PCa, likely linked to promoter methylation; PRKY promoter methylation showed high specificity for early PCa and may outperform PSA, mpMRI, and other molecular biomarkers. 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\n[https://doi.org/10.1080/1750191](https://doi.org/10.1080/1750191)1.2024.2365625  \nRESEARCH ARTICLE     \nPromoter hypermethylation ofY-chromosome gene PRKYas a potential biomarker for the early diagnosis of prostate cancer  \nZheng Dai‡, a, b, Hongbing Chen‡,b, Kaiwen Feng‡, a, Tuoxin Lia, Weifeng Liua, Yibin Zhoua, Dongrong Yanga, Boxin Xue* , a and Jin Zhu** , a  \na Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China; bDepartment of Urology, The Third Affiliated Hospital of Anhui Medical University, Hefei, 230061, China  \nABSTRACT  \nAim: To develop a methylation marker of Y-chromosome gene in the early diagnosis of prostate cancer (PCa) .  \nMaterials & 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.  \nConclusion: PRKY promoter methylation may be a potential marker for the early and accurate diagnosis of PCa.  \nTWEETABLE ABSTRACT  \nDeveloping 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.  \nARTICLE HISTORY  \nReceived 17 January 2022 Accepted 4 June 2024  \nKEYWORDS  \nEarly diagnosis; PRKY; Promoter methylation; Prostate cancer;  \nY-chromosome  \n1. Background  \nProstate cancer (PCa) is the second leading cause of cancer death among men in USA, with nearly 260,000 new cases and 30,000 deaths, according to cancer statistics in 2022 [1] . PCa patients have no apparent symptoms in the early stage and most are in the middle or late stages at the initial diagnosis. Some patients quickly develop metastatic castration-resistant prostate cancer after treatment, which is highly invasive, incurable and has a poor prognosis [2] . Therefore, early diagnosis and treatment are important for PCa patients. Currently, the routine screening methods for PCa are serum prostate-specific antigen (PSA) and digital rectal examination (DRE) [3] . DRE can only palpate the part of the prostate adjacent to the rectum and the results are affected by the subjective judgment of clinicians; consequently, approximately 20% of PCa patients have a positive [4] . PSA screening is the primary method for detecting PCa early, but its  \nlow specificity frequently leads to unnecessary biopsies and overtreatment [5] . Previous studies have confirmed that multiparameter MRI (mpMRI) has high accuracy for diagnosing PCa, especially for clinically significant PCa, but for T1 or T2 tumors and patients in the PSA gray zone, mpMRI still has a certain rate of missed diagnosis [6]. The gold standard for PCa diagnosis is a prostate biopsy, but as an invasive procedure, it causes significant suffering for patients, including rectal bleeding, pain in the operating area, sepsis and other complications [7] . Therefore, it is warranted to search for a noninvasive, highly sensitive  \nbiomarker that can be used to diagnose early PCa.  \nDNA methylation plays an important role in the biological behavior of human malignant tumors. DNA methylation status of certain genes can be used as potential tumor biomarkers for risk prediction, diagnosis, prognosis and efficacy assessment of cancer [8]. Aberrant DNA methylation primarily includes promoter hypermethylation of the tumor suppressor gene, hypomethy-  \nCONTACT Boxin Xue  [18994392817@163.com](18994392817@163.com);","cbCaim7QDL2vJb8b","https://ap.wps.com/l/cbCaim7QDL2vJb8b","pdf",2203438,16,"English","# Background\n## DNA methylation and need for noninvasive biomarkers\n# Results and conclusions","[{\"question\":\"What is the goal of this study on PRKY in prostate cancer?\",\"answer\":\"To develop a methylation-based marker using the Y-chromosome gene PRKY for early diagnosis of prostate cancer (PCa).\"},{\"question\":\"How were PRKY methylation and diagnostic value validated?\",\"answer\":\"Bioinformatics analysis identified PRKY expression and promoter methylation, and single-center experiments were conducted to validate the diagnostic value of PRKY promoter methylation in PCa.\"},{\"question\":\"Why is PRKY promoter methylation considered potentially better than PSA or mpMRI?\",\"answer\":\"The results report high specificity for early PCa and suggest it may be superior to PSA, mpMRI, and other molecular biomarkers mentioned in the study.\"}]","Promoter hypermethylation of Y-chromosome gene PRKY as a potential biomarker for the early diagnosis of prostate cancer - Research Article | PDF",1790022050]