Promoting cell proliferation, cell cycle progression, and glycolysis: Glycometabolism-related genes act as prognostic signatures for prostate cancer

The Warburg effect seen in most solid tumors occurs only in the late stages of prostate cancer (PCa). Currently, the management of patients with low-risk localized PCa and patients after radical therapy remains a challenge. Our objective here was to evaluate glycometabolism-related genes as prognostic signatures for PCa.

The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases and glycometabolism-related gene sets were obtained online. Glycometabolic prognostic signatures were identified and validated in a TCGA cohort and tested in an ICGC cohort. We used the gene set enrichment analysis to reveal biological processes associated with the glycometabolism-related signatures. Novel glycometabolism-related genes were selected for verifying their oncogenic phenotypes in vitro.

Two glycometabolic prognostic signatures were applied respectively to construct risk score formulas for PCa. Survival and receiver operating characteristic curve analyses were performed to detect the value of these prognostic signatures. We performed univariate and multivariate Cox regression analyses in the TCGA cohort, demonstrating the independence of the prognostic signatures. Three glycometabolism-related genes were found to be novel PCa-associated genes. These were shown to affect proliferation, cell cycle progression, and glycolysis of DU145 and PC3 cells in different degrees.

The present research represents the first glycometabolic and high-throughput investigation on PCa, revealing potential biomarkers and treatment targets. We confirm the vital role of glycometabolism in PCa and provide essential resources for future exploration of metabolism in PCa.