Hybrid Metabolic Activity-Related Prognostic Model and Its Effect on Tumor in Renal Cell Carcinoma

Abstract

Background. Tumor cells with a hybrid metabolic state, in which glycolysis and oxidative phosphorylation (OXPHOS) can be used, usually have a strong ability to adapt to different stress environments due to their metabolic plasticity. However, few studies on tumor cells with this phenotype have been conducted in the field of renal cell carcinoma (RCC). Methods. The metabolic pathway (glycolysis, OXPHOS) related gene sets were obtained from the Molecular Signatures Database (V7.5.1). The gene expression matrix, clinical information, and mutation data were obtained by Perl programming language (5.32.0) mining, the Cancer Genome Atlas and International Cancer Genome Consortium database. Gene Set Enrichment Analysis (GSEA) software (4.0.3) was utilised to analyse glycolysis-related gene sets. Analysis of survival, immune infiltration, mutation, etc. was performed using the R programming language (4.1.0). Results. Eight genes that are highly associated with glycolysis and OXHPOS were used to construct the cox proportional hazards model, and risk scores were calculated based on this to predict the prognosis of clear cell RCC patients and to classify patients into risk groups. Gene Ontology, the Kyoto Encyclopaedia of Genes and Genomes, and GSEA were analysed according to the differential genes to investigate the signal pathways related to the hybrid metabolic state. Immunoinfiltration analysis revealed that CD8+T cells, M2 macrophages, etc., had significant differences in infiltration. In addition, the analysis of mutation data showed significant differences in the number of mutations of PBRM1, SETD2, and BAP1 between groups. Cell experiments demonstrated that the DLD gene expression was abnormally high in various tumor cells and is associated with the strong migration ability of RCC. Conclusions. We successfully constructed a risk score system based on glycolysis and OXPHOS-related genes to predict the prognosis of RCC patients. Bioinformatics analysis and cell experiments also revealed the effect of the hybrid metabolic activity on the migration ability and immune activity of RCC and the possible therapeutic targets for patients.