Construction and multi-omics analysis of ccRCC mitochondrial related gene machine learning model and validate of key gene FKBP10.

BACKGROUND

Clear cell renal cell carcinoma represents the most prevalent histological subtype of renal malignancy Emerging evidence underscores the critical involvement of mitochondrial dysfunction in oncogenesis and tumor progression. In this study, we systematically identified and characterized mitochondrial-associated proteins participating in fundamental biological processes, with the objective of elucidating their mechanistic contributions to ccRCC pathogenesis.

METHOD: Through integrative analysis of multi-omics data from TCGA-KIRC and GEO datasets, we systematically evaluated the prognostic value of mitochondrial-associated differentially expressed genes derived from the MitoCarta3.0 database. Employing an ensemble machine learning approach encompassing 10 base algorithms and their combinatorial variants, we developed and optimized a robust prognostic risk model. Subsequent experimental validation focused on the core model gene FKBP10, investigating its functional role in ccRCC pathogenesis through comprehensive in vivo analyses.

RESULT: We identified 102 mitochondrial-related differentially expressed genes showing significant tumor-normal tissue expression differences and strong prognostic associations. The LASSO+GBM algorithm was selected as the optimal model, from which we derived 7 core prognostic genes. Comprehensive characterization of high- and low-risk groups revealed distinct patterns in pathway activation, mutational profiles, immune microenvironment composition, and therapeutic vulnerabilities. Experimental validation confirmed that the key gene FKBP10 promotes malignant phenotypes in tumor cells through IL-6/JAK/STAT3 pathway activation.