Abstract A111: Urine-based gene expression panels with focus on prostate cancer in African Americans

Abstract

Abstract Introduction: Prostate cancer (CaP) affects 1 in 7 men in their lifetime. African American (AA) men have significantly higher incidence and mortality from CaP compared to Caucasian American (CA) men. We and others have also noted that the genes commonly overexpressed in CaP (e.g., ERG) and currently used as diagnostic markers exhibit much lower frequency and more heterogeneity in AA men. The goals of this study are to develop CaP diagnostic/prognostic marker panels that takes into account race-associated differences in molecular alterations. Here we evaluated a panel of CaP associated genes using regular (non-DRE) urine from AA and CA CaP for discriminating between high-grade (Gleason score [GS], 7-10) and low-grade disease (GS, 6) and cancer negative biopsy. Methods: The quantitative expression assay protocols have been developed for noninvasive detection of candidate genes in exosomal RNAs from regular urine. The selected genes were reverse transcribed in a single reaction using gene-specific primer pool (GSP) followed by preamplification and PCR-based assay of all target genes. Results: Regular urine exosomal RNA-based assays were developed and optimized for PSGR, DLX1, HOXC4, NKX2-3, COL10A1, HOXC6, PCA3, PCGEM1, PCAT1, CTBP1, SChLAP1, ERG and SPDEF. All markers have been evaluated in a pilot study of 72 subjects undergoing diagnostic biopsies. For AA patients a sensitivity of 88.2%, specificity of 83.3%, and AUC of 0.81 were achieved for the panel (PCA3, PCGEM1, HOXC6 and SChLAP1). Consistent with numerous studies, ERG and PCA3 panel was optimal for CA patients. Preliminary analysis showed that 3 markers were found to be associated with improved discrimination between GS7 or greater and GS6 (AUC 0.78 for ERG; AUC 0.72 for PSGR and AUC 0.72 for SChLaP1) in AA CaP. In CA patients, PCA3 gave an AUC of 0.76 for predicting high-grade from low-grade disease. Analysis of an additional 100 patients is in progress. Conclusions: Given the genomic difference of prostate cancer among different race/ethnicity, this study highlights the potential for developing CaP biomarker panels in the context of race for enhancing precision medicine through improved CaP diagnosis/prognosis Citation Format: Indu Kohaar, Sreedatta Banerjee, Yongmei Chen, Amina Ali, Jacob Kagan, Sudhir Srivastava, Jennifer Cullen, Inger Rosner, Shiv Srivastava, Gyorgy Petrovics. Urine-based gene expression panels with focus on prostate cancer in African Americans [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A111.