Abstract 510: Molecular subtypes related to prostate cancer disparities and disease outcome in African American and European American patients

Abstract

Abstract Prostate cancer disproportionately affects African American (AAM) men, yet present biomarkers do not factor in prostate cancer racial disparity. The objective of this study was to identify biomarkers with potential benefits to AAM prostate cancer patients. Differentially expressed genes (DEG) analysis coupled with gene set enrichment analysis (GSEA) and leading-edge genes analysis showed that the keratin family of genes, including KRT8, KRT15, KRT19, KRT34, and KRT80, constituted the single most prominent family of genes enriched in AAM compared to European American (EAM) prostate cancer cell lines. In prostate cancer patients (TCGA and MSKCC patient cohorts), only KRT8, KRT15, and KRT19 expression were relatively higher in AAM than in EAM. The differences in the expression of KRT15 and KRT19, but not KRT8, were enhanced by Gleason score and ERG fusion status; in low Gleason (Gleason ≤ 6 [TCGA cohort] and Gleason ≤ 7 [MSKCC cohort]), the expression of KRT15 and KRT19 was significantly (p ≤ 0.05) higher in AAM than in EAM patients. Survival analysis revealed that high expression of KRT15 and KRT19 was associated with increased risk of biochemical recurrence in low Gleason category patients in the TCGA patient cohort. Interestingly, KRT15 and KRT19 expression was associated with an increased risk of death in the metastatic prostate adenocarcinoma (SU2C/PCF Dream Team, PNAS 2019) cohort, suggesting the potential to predict the risks of disease recurrence and death in the low Gleason category and advanced disease conditions respectively. Gene set enrichment analysis revealed known oncogenic gene signatures, including KRAS and ERBB2, to be enriched in patients expressing high KRT15 and KRT19. Furthermore, high KRT15 and KRT19 were linked to the basal and LumA prostate cancer subtypes associated with poor postoperative androgen deprivation therapy (ADT) response compared to the LumB subtype. Taken together, the present study identifies genes with high expression in AAM than in EAM prostate cancer. The identified genes are linked to oncogenic gene signatures, including KRAS and ERBB2, and to basal and LumA prostate cancer subtypes that are associated with poor postoperative ADT response. The study, therefore, reveals biomarkers with the potential to address biomarker bias in prostate cancer diagnosis and/or prognosis. Future studies would explore the diagnostic and/or prognostic potential of identified markers in prostate cancer tissue samples. Citation Format: Joakin Opeli Mori, Jason White, Balasubramanyam Karanam, Clayton Yates, Honghe Wang. Molecular subtypes related to prostate cancer disparities and disease outcome in African American and European American patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 510.