Abstract A064: Prediction of positive prostate biopsy is significantly improved in Black and Hispanic men when serum PVT1 exon 9 copy number is combined with 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 that target the unique genetic make-up of 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 PCa across different racial populations. Methodology Forty serum samples from White, Hispanic, and Black men, 50 percent of whom had PCa, were analyzed to obtain copy numbers for PVT1 exons 4A, 4B, and 9. Seven logistic regression models were developed to predict PCa using single 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 PCa for all races, our model with only PVT1 exon 9 achieved the highest median AUC of 0.71, which was better than the AUC of 0.63 obtained with just PSA. When PSA and PVT1 exon 9 were combined, the median AUC increased to 0.75. Combining all three biomarkers with PSA increased the median AUC to 0.813. For the Black and Hispanic subpopulation, PVT1 exon 9 achieved the highest AUC of 0.92 which was significantly higher than the median AUC of 0.63 achieved with PSA. No significant change in AUC was observed when the PVT1 biomarkers were combined with PSA. Conclusion Our results show that PVT1 exon 9 is more accurate than PSA in predicting PCa, achieving near perfect accuracy within the Black and Hispanic subpopulation. Whereas combining PSA with PVT1 biomarkers improved the performance of PSA for all races, no significant improvement in PSA’s performance was observed in Black and Hispanic subpopulations. Thus, PVT1 exon 9 may hold the key to reducing disparity in PCa detection among moAA while improving the predictive accuracy of PSA for the general population Citation Format: Emmanuel Owusu Asante-Asamani, Dinuka Sewandi De Silva, Gargi Pal, Michael Liss, Robin Leach, Olorunseun Ogunwobi. Prediction of positive prostate biopsy is significantly improved in Black and Hispanic men when serum PVT1 exon 9 copy number is combined with 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 A064.