Metabolic pathways enriched according to ERG status are associated with biochemical recurrence in Hispanic/Latino patients with prostate cancer

Abstract

Abstract Background The role of ERG‐status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG‐status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients. Methods RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA‐sequencing. ERGhigh/ERGlow tumor groups were determined based on the 1.5‐fold change median expression in non‐tumor samples. DEGs with a False Discovery Rate (FDR) 2 were identified between ERGhigh and ERGlow tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed to evaluate biochemical recurrence (BCR)‐free survival. Results The identification of 150 DEGs between ERGhigh and ERGlow tumors revealed clustering of most of the non‐BCR cases (60%) into de ERGhigh group and most of the BCR cases (60.8%) in ERGlow group. Kaplan–Meier survival curves showed a worst BCR‐free survival for ERGlow patients, and a significant reduced risk of BCR was observed for ERGhigh cases (OR = 0.29 (95%CI, 0.10–0.8)). Enrichment pathway analysis identified metabolic‐related pathways, such as the renin‐angiotensin system and angiotensin maturation system, the linoleic acid metabolism, and polyamines metabolism in these ERG groups. Conclusions ERGlow tumor cases were associated with poor BCR‐free survival in our Hispanic/Latino patients, with metabolism‐related pathways altered in the BCR progression. Impact Our findings suggest the need to dissect the role of diet, metabolism, and lifestyle as risk factors for more aggressive PCa subtypes.

Keywords

• biochemical recurrence
• differentially expressed genes
• ERG subtypes
• prostatic neoplasms
• signaling pathways