Abstract 1503: Molecular subtypes in prostate cancer with differential prognosis and tumor biology in Hispanic patients
Authors: Natalia Lizeth Acosta Vega, Rodolfo Varela, Jorge A. Mesa, Jone Garay, Melody Baddoo, Jovanny Zabaleta, Alba L. Combita-Rojas, María C. Sanabria-Salas
Journal: Cancer Research (2020)

Abstract Purpose: Clinical progression of localized prostate cancer (PCa) is highly variable mainly because of its multifocality and heterogeneity nature. Recent advances in emerging techniques have allowed to explore the molecular basis of PCa allowing the identification of molecular subtypes for primary PCa based on genetic alterations. The most prevalent subtype harbors rearrangements between the androgen-regulated promoter of TMPRSS2 with a member of the ETS family of transcription factors, the oncogene ERG, present in about 40%-50% of cases, and leading to increased expression of ERG. Here, we characterized the two main molecular subtypes, tumors overexpressing ERG and tumors with downregulated ERG, in localized PCa from Hispanic patients and determined the association of these subtypes with the prognosis of biochemical recurrence (BCR). Methods: A total of 89 Hispanic cases with localized PCa were included. RNA from formalin-fixed paraffin-embedded tissues of radical prostatectomy (RP) was extracted and sequenced. We made differential expression analysis between ERGhigh and ERGlow cases and significant genes were submitted to MetaCore for enrichment analysis. Association with clinical and pathological variables was done and the impact of ERG subtypes on prognosis was determined by Kaplan-Meir analysis, Log-rank test and Cox proportional hazard regression, taking 5-year BCR-free survival as the event. Results: Comparison between ERGhigh and ERGlow tumors showed 150 differentially expressed genes (DEGs) that revealed enriched pathways related with the angiotensin system and its signal transduction, Notch and NF-κB pathways, Beta-catenin-dependent transcription regulation in colorectal cancer, mTORC1 upstream signaling, linoleic acid metabolism, and polyamine metabolism. The renin-angiotensin system is implicated in PCa development since it activates MAPK, STAT3 and VEGF, ultimately stimulating proliferation and formation of blood vessels. ERGlow demonstrated to be associated with higher Gleason Grade Groups at RP and with BCR, and log-rank test showed correlation with worse BCR-free survival within 5-years after RP, while ERGhigh subtype presented a better BCR-free survival. Conclusions: Our analysis illustrates different signaling pathways between the two main molecular subtypes in PCa, ERGhigh and ERGlow, which associates with different prognosis in Hispanic patients with localized PCa. Citation Format: Natalia Lizeth Acosta Vega, Rodolfo Varela, Jorge A. Mesa, Jone Garay, Melody Baddoo, Jovanny Zabaleta, Alba L. Combita-Rojas, María C. Sanabria-Salas. Molecular subtypes in prostate cancer with differential prognosis and tumor biology in Hispanic patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1503.