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

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. ERG ( high )/ERG ( low ) tumor groups were determined based on the 1.5‐fold change median expression in non‐tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change >2 were identified between ERG ( high ) and ERG ( low ) 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 ERG ( high ) and ERG ( low ) tumors revealed clustering of most of the non‐BCR cases (60%) into de ERG ( high ) group and most of the BCR cases (60.8%) in ERG ( low ) group. Kaplan–Meier survival curves showed a worst BCR‐free survival for ERG ( low ) patients, and a significant reduced risk of BCR was observed for ERG ( high ) 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: ERG ( low ) 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.