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

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. 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.

Keywords: ERG subtypes; biochemical recurrence; differentially expressed genes; prostatic neoplasms; signaling pathways.