Metabolic pathways enriched according to ERG status are associated with biochemical recurrence in Hispanic/Latino patients with prostate cancer. (3rd November 2022)

• Record Type: Journal Article
• Authors: Acosta‐Vega, Natalia L.; Varela, Rodolfo; Mesa, Jorge Andrés; Garai, Jone; Baddoo, Melody C.; Gómez‐Gutiérrez, Alberto; Serrano‐Gómez, Silvia J.; Lemus, Marcela Nuñez; Serrano, Martha Lucía; Zabaleta, Jovanny; Combita, Alba L.; Sanabria‐Salas, María Carolina
• Is Part Of: Cancer medicine. Volume 12:Number 4(2023)
• Page Start: 4306
• Page End: 4320
• Publication Date: 2022-11-03
• Subjects: biochemical recurrence -- differentially expressed genes -- ERG subtypes -- prostatic neoplasms -- signaling pathways; 616.994005
• DOI: 10.1002/cam4.5301
• Languages: English
• ISSNs: 2045-7634

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. 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. Abstract : Differentially expressed genes (DEGs) between ERG high and ERG low tumors revealed clustering of most of the non‐BCR cases into de ERG high group and most of the BCR cases in ERG low group. Subsequent analyses confirmed an association between ERG status with BCR, showing a worst BCR‐free survival for ERG low patients compared to the ERG high group. Enrichment pathway analysis of the 150 DEGs identified an important participation of metabolic‐related pathways in the BCR progression.