Identification of prostate cancer by urinary DLX1/HOXC6 expression in Chinese population with prostate-specific antigen levels of 4-10 ng/mL.

Early diagnosis of prostate cancer (PCa) is crucial, but the widely used prostate-specific antigen (PSA) biomarker lacks specificity in the 4.0–10.0 ng/mL grey zone, causing many unnecessary biopsies. This study assessed urinary DLX1/HOXC6 mRNA’s diagnostic performance for PCa (both low-grade and high-grade) in Chinese men with grey-zone PSA. 584 participants with PSA 4.0–10.0 ng/mL were prospectively enrolled in two cohorts (Cohort A: n = 258; Cohort B: n = 326). Urine samples were analyzed via RT-PCR to detect DLX1/HOXC6 expression levels. A DH-Score model was developed by logistic regression and its diagnostic performance was validated. The RT-PCR assay demonstrated excellent precision, linearity, and stability against common interferents. In Cohort A, the DH-Score achieved an area under the receiver operating characteristic curve (AUC) of 0.951 (95% CI 0.917–0.974), with a sensitivity of 85.6% and a specificity of 89.1%. Validation in Cohort B showed consistent performance (AUC = 0.933, sensitivity = 84.3%, specificity = 88.7%), demonstrating robust accuracy. A negative predictive value of 85–89% could reduce unnecessary biopsies by excluding benign cases in the gray zone of the PSA. In Conclusion, DH-Score offers a non-invasive, accurate PCa risk stratification in the PSA grey zone, reducing unnecessary biopsies while preserving high diagnostic efficacy in Chinese men.