Identification and validation of critical mitochondrial hub genes for prostate cancer

Prostate cancer (PCa) is one of the most common malignant tumors in men. In recent years, mitochondrial dysfunction has been found to be closely related to cancer progression. However, the role of mitochondria-related genes in PCa remains unclear. The aim of the present study was to discover novel biomarkers based on differentially expressed mitochondrial-related genes (DeMRGs) to aid in PCa diagnosis. In the present study, gene expression data from the Gene Expression Omnibus and The Cancer Genome Atlas databases were combined with a mitochondrial-related gene list provided by the MitoCarta database to identify DeMRGs. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis were then used to investigate the functions and related pathways of these DeMRGs. Subsequently, Cytoscape software and the STRING website were used to explore the transcription factors and microRNAs related to the DeMRGs. The degree of infiltration of immune cells in the immune landscape of patients with PCa and the controls was assessed using CIBERSORT. Finally, the correlation between characteristic DeMRGs and immune cell infiltration and mitochondrial respiration was analyzed. The results indicated that 6 characteristic genes, including acetyl-CoA carboxylase β (ACACB), pyruvate dehydrogenase kinase 4 (PDK4), glycine amidinotransferase (GATM), methylcrotonyl-CoA carboxylase subunit 2, mitochondrial ribosomal protein L12 (MRPL12) and fatty acid synthase, were identified from the 60 DeMRGs. The results showed a close association between the characteristic DeMRGs and immune infiltrating cells. In addition, it was found that MRPL12, PDK4, ACACB and GATM were correlated with mitochondrial respiration. These 4 genes were selected as hub genes as they are closely related to gluconeogenesis, the tricarboxylic acid cycle, lipid metabolism, amino acid metabolism and other mitochondrial metabolic pathways in PCa. In conclusion, 4 novel mitochondrial-related gene signatures that influence mitochondrial metabolism within the immune microenvironment were identified in PCa.