Exploring the prognostic significance of lactate-mitochondria-related genes in prostate cancer.

Abstract

Prostate cancer (PCa) is a common and serious health issue among older men globally. Metabolic reprogramming, particularly involving lactate and mitochondria, plays a key role in PCa progression, but studies linking these factors to prognosis are limited. To identify novel prognostic markers of PCa based on lactate-mitochondria-related genes (LMRGs), RNA sequencing data and clinical information of PCa from The Cancer Genome Atlas (TCGA) and the cBioPortal database were used to construct a lactate-mitochondria-related risk signature. Here, we established a novel nine-LMRG risk signature for PCa, and Kaplan-Meier curves confirmed a worse prognosis for high-risk subgroups in the TCGA dataset. Meanwhile, a nomogram that effectively predicts the prognosis of PCa patients was also constructed. Next, close associations between the lactate-mitochondria-related signature and the immune microenvironment were examined to clarify the role of LMRGs in shaping the immune landscape. Furthermore, as the only lactate-related gene among the nine key prognostic risk genes, myeloperoxidase (MPO) was identified as a key factor that mediates lactate production in vitro and in vivo through attenuation of the glycolytic pathway. More importantly, MPO significantly inhibited PCa cell migration, invasion, and epithelial-mesenchymal transition (EMT), indicating its potential as an anticancer gene. Additionally, PCa with high MPO expression is highly sensitive to chemotherapeutic agents and mitochondrial inhibitors, highlighting its potential as an improved therapeutic strategy for PCa management.