Abstract A065: Serum PVT1 exons 4A and 4B copy numbers are better predictors of high-grade prostate cancer in Black and Hispanic men than serum prostate specific antigen

Abstract

Abstract Background Men of African ancestry (moAA) experience the highest incidence and mortality rates of prostate Cancer (PCa) in the United States, where 1 in 8 men are expected to be diagnosed with the disease in their lifetime. Yet, most biomarkers used in PCa screening today, which are based on prostate specific antigen (PSA), are developed and validated in predominantly White populations with weak or nonexistent validation in moAA, making moAA more likely to be subjected to unnecessary prostate biopsies. To reduce this disparity in PCa detection and management, there is a critical need for new biomarkers with demonstrated usefulness in moAA. We recently showed that plasmacytoma variant translocation 1 (PVT1), exons 4A, 4B, and 9 are overexpressed in the prostate tissues and detected in higher copy numbers in serum of moAA with PCa. In this study, we investigated the predictive power of these potential biomarkers in detecting high-grade PCa across different racial populations. Methodology Forty serum samples from White, Hispanic, and Black men, 50% of whom had PCa with 25% showing high-grade PCa, were analyzed to obtain copy numbers for PVT1 exons 4A, 4B, and 9. Seven logistic regression models were developed to predict PCa using individual PTV1 biomarkers, all pairwise combinations of biomarkers and all three biomarkers. The median area under the receiver operator characteristic curve (AUC) was used to measure the predictive accuracy of each model after a repeated, stratified k-fold cross validation. Model accuracy was first evaluated using data from all races and then for just the Black and Hispanic subpopulation. Our best performing models were compared with PSA as a predictor of PCa. We also evaluated the predictive accuracy of composite models that combined our biomarkers with PSA. Results In predicting high-grade PCa for all races, PSA had a median AUC of 0.58. All our PVT1 biomarkers had an AUC greater than 0.64, which was better than PSA. When PSA and PVT1 exon 4B were combined, the median AUC of PSA increased to 0.67, other PTV1 biomarkers did not improve the AUC of PSA. For the Black and Hispanic subpopulation, PVT1 exon 4A achieved the highest median AUC of 0.92 which was significantly higher than the median AUC of 0.33 achieved with PSA. The model with Exon 4A and Exon 4B as well as all three biomarkers achieved perfect discrimination (AUC of 1.0). We were also able to obtain perfect discrimination when PVT1 exon 4A was combined with PSA (AUC: 1.0). Conclusion Our results show that PVT1 exon 4A is more accurate than PSA in predicting high-grade PCa in Black and Hispanic subpopulations, achieving perfect discrimination when combined with PSA. Significant improvement in PSA’s predictability is observed in all races when combined with PTV1 exon 4B. Thus, PVT1 exon 4A and PVT1 exon 4B may hold the key to reducing disparity in high-grade PCa detection among moAA while improving the predictive accuracy of PSA for the general population. Citation Format: Emmanuel Owusu Asante-Asamani, Dinuka S.H. Sewandi De Silva, Gargi Pal, Michael Liss, Robin Leach, Olorunseun O. Ogunwobi. Serum PVT1 exons 4A and 4B copy numbers are better predictors of high-grade prostate cancer in Black and Hispanic men than serum prostate specific antigen [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A065.