Adaptive mitochondrial modules: Going with the flow of cancer-specific metabolic rewiring
Mehmet Taha YildizDepartment of Child Development, University of Health Sciences, Hamidiye Faculty of Health Sciences, Istanbul, TürkiyeINTRODUCTION: Mitochondrial gene networks constitute a fundamental subsystem of cellular homeostasis, integrating bioenergetic, metabolic, and signaling functions. In cancer, the rewiring of these networks represents a critical mechanism of metabolic adaptation, enabling tumor cells to sustain growth and survival under diverse microenvironmental constraints. To systematically characterize these alterations, we analyzed transcriptomic data from The Cancer Genome Atlas (TCGA) with a specific focus on mitochondrial genes, aiming to uncover cancer-type-specific patterns of differential expression and their potential biological implications.
METHODS: Transcriptomic data from The Cancer Genome Atlas (TCGA) were analysed to identify diferential expression patterns in mitochondrial genes. Weighted Gene Coexpression Network Analysis (WGCNA) was applied to detect coexpressed gene modules. The biological relevance of these modules was assessed through functional enrichment analysis and survival modelling using Cox regression and Kaplan–Meier estimations. Dimensionality reduction techniques including PCA and UMAP were used to evaluate module-driven clustering patterns across cancer types.
RESULTS: Seven mitochondrial gene modules were identifed, six of which demonstrated signifcant associations with specific cancer types. Modules ME2, ME4, ME5, ME6, and ME7 were associated with improved overall survival, while ME3 correlated with poorer prognosis. Functional enrichment analyses revealed distinct mitochondrial processes including oxidative phosphorylation, apoptosis, fatty acid β-oxidation, and ketone body metabolism. Dimensionality reduction analyses supported the presence of module-specifc expression patterns with cancer-type-dependent clustering.
DISCUSSION AND CONCLUSION: The observed cancer-type-specific expression and prognostic associations of mitochondrial gene networks reflect their central involvement in the metabolic flexibility of tumors. By underscoring the clinical and biological significance of mitochondrial subsystems, these findings suggest that they may serve not only as prognostic markers but also as promising targets for therapeutic modulation.
Manuscript Language: English