Mitochondrial metabolism-related signature depicts immunophenotype and predicts therapeutic response in testicular germ cell tumors

Abstract

In recent years, there has been growing evidence linking mitochondrial dysfunction to the development and progression of cancer. However, the role of mitochondrial metabolism-related genes (MMRGs) in testicular germ cell tumor (TGCT) remains unclear. We downloaded clinical pathology, transcriptome, and somatic mutation data for TGCT from public databases and conducted univariate Cox regression analysis to investigate prognostic correlations. We also used consensus clustering to identify molecular subtypes, comparing differential expression genes, biological processes, Kyoto Encyclopedia of Genes and Genomes pathways, mutations, prognosis, immune infiltration, drug sensitivity, and immune therapeutic response between these subtypes. We constructed multi-gene risk features and nomograms for TGCT prognosis. Fifteen MMRGs were significantly correlated with progression-free survival in TGCT patients. Based on these genes, we identified 2 molecular subtypes which showed significant differences in somatic mutations, prognosis, and immune cell infiltration. These subtypes could also indicate drug sensitivity and immune therapeutic response; the subtype with poor prognosis showed a higher potential benefit from some drugs and immunotherapy. Abnormalities in immune-related biological processes and extracellular matrix as well as Kyoto Encyclopedia of Genes and Genomes pathways such as PI3K-AKT signaling pathway, pat5hways in cancer, primary immunodeficiency, and neutrophil extracellular trap formation were associated with significant differences in phenotypes among subtypes. Finally, we constructed an 8-gene TGCT risk feature based on differential expression genes between subtypes which performed well in TGCT patient prognostic evaluation. Our study elucidated the prognostic correlation between MMRGs and TGCT and established MMRG-derived molecular subtypes and risk features for personalized treatment of TGCT which have potential clinical application value.