Evaluation of Loss of the Y Chromosome in Peripheral Blood as a Biomarker for Prostate Cancer

BACKGROUND: Prostate cancer (PCa) is the most common malignant tumor in men, but the widely used prostate-specific antigen (PSA) test has limited diagnostic accuracy. Research proposes that the loss of the Y chromosome (LOY) may affect the occurrence and development of prostate cancer, aiming to assess its potential as a diagnostic biomarker to improve the accuracy of prostate cancer detection and clinical management. METHODS: LOY levels were measured using droplet digital polymerase chain reaction (ddPCR) method, integrating relevant clinical indicators to evaluate the potential clinical significance of LOY in PCa. Logistic regression was employed to estimate risk prediction capability of LOY, and model performance was validated through bootstrapping. FINDINGS: 131 men patients were enrolled in this study whose PSA level exceeding 4.0 ng/ml and underwent prostate biopsies. According to post-biopsy pathological results, subjects were classified into normal and cancer groups. LOY levels were significantly higher in the cancer group than in the normal group (p < 0.001). LOY levels show a consistent increase with advancing AJCC clinical stage and escalating PI-RADS scores. LOY is a promising biomarker for PCa (AUC = 0.898). Clinical decision curve analyzes demonstrated that incorporating LOY into each conventional model provided greater clinical benefit compared with the original model. INTERPRETATION: In biopsy patients, the LOY levels in the cancer group were higher than those in the normal group, and this was more pronounced in patients at advanced clinical stages. LOY levels have strong diagnostic efficacy for PCa, indicating that LOY may serve as an auxiliary biomarker for early PCa diagnosis.