the Prediction of Positive Prostate Biopsies in Men is Significantly Enhanced when PVT1 Exon 4A is Combined with Serum Prostate Specific Antigen (PSA)

Prostate cancer (PCa) remains a significant public health challenge, ranking as the second leading cause of cancer-related deaths among men in the United States. Current diagnostic approaches, predominantly centered on prostate-specific antigen (PSA) testing, often lead to overdiagnosis and unnecessary biopsies. The long nonprotein coding gene, PVT1 (plasmacytoma variant translocation 1), has shown promise as a biomarker, being upregulated in PCa and associated with disease progression and metastasis. This study investigates the potential of incorporating PVT1 biomarkers to improve diagnostic accuracy for PCa detection, focusing on both the general population and men of African ancestry, who are disproportionately impacted by PCa incidence and mortality.A total of 144 serum samples were analyzed, with 72 samples from men diagnosed with PCa and 72 from men without cancer. Serum levels of PVT1 Exons 4A, 4B, and 9 were quantified using digital PCR. Multiple logistic regression models were developed to predict cancer status based on PSA alone, PVT1 biomarkers alone, and combinations of PSA with PVT1 biomarkers. Model performance was assessed using stratified k-fold cross-validation, with comparisons made using likelihood ratio tests, and z-tests for statistical significance.The results show that combining PSA with PVT1 Exon 4A improves specificity in predicting cancer status in the general population from 0.45 to 0.54 while maintaining sensitivity at 0.81. Within the subpopulation of men of African Ancestry, PVT1 Exon 4A alone achieves an accuracy of 0.75 with a sensitivity of 1.0 and specificity of 0.5 compared to PSA alone which had an accuracy of 0.38, sensitivity of 0.5 and specificity of 0.25.This study underscores the potential clinical utility of integrating PVT1 biomarkers into prostate cancer screening programs. The inclusion of Exon 4A enhanced PSA-based prediction by addressing its limitations in overdiagnosis and unnecessary biopsies, providing a balanced improvement in diagnostic performance. By improving the accuracy of PCa detection while reducing the burden of overdiagnosis, this approach provides significant value for healthcare providers, diagnostic laboratories, and insurers aiming to enhance early detection and equitable screening outcomes. Tinovimba L. Hove, Rachel E. Sexton, Michael Liss, Robin Leach, Emmanuel Asante-Asamani, Olorunseun O. Ogunwobi. The prediction of positive prostate biopsies in men is significantly enhanced when PVT1 Exon 4A is combined with serum Prostate Specific Antigen (PSA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1058.