Downregulated expression of SLC22A8 promotes the metabolic disorders of clear cell renal cell carcinoma
Objective To explore the key genes associated with the development and progression of clear cell renal cell carcinoma(ccRCC),and to study their potential effects and prognostic value.Methods From November 2022,the differentially expressed genes(DEGs)of GSE6344 and GSE53757 in the GEO database were screened by CEO2R online analysis tool to obtain common DEGs by in-tersection.Next,a protein interaction network were constructed by the STRING database and Cytohubba program was applied to select the genes with TOP5 protein interaction degree as key genes,following which these key genes were submitted to survival analysis to search which was associated with the prognosis of ccRCC.Subsequently,the cBioportal database was used for gene alteration analysis to derive significantly mutated key genes,DAVID database was used for functional enrichment and pathway analysis of key genes with significant mutations,and the differential expression of key gene proteins with significant mutations was confirmed in the UALCAN and HPA database.The above analysis process was completed on December 2022.Results There were 198 DEGs and 183 DEGs screened from GSE6344 and GSE53757,and 63 common DEGs(41 up-regulated genes and 22 down-regulated genes)were obtained by taking intersections.Furthermore,the protein relationship network of the 63 co-expressed DEGs was analyzed by applying Cytohubba program to obtain five key genes:SMIM5,TMEM213,SLC12A3,SLC22A8 and SLC13A3,all of which were down-regulated genes.Sur-vival analysis revealed that SLC12A3,SLC22A8,SLC13A3 and TMEM213 were associated with ccRCC prognosis.The gene alteration analysis suggested that SLC22A8 was the key gene for prominent mutation and its enrichment analysis was mainly related to various regulated processes such as carbohydrate metabolism,mitochondrial function and peroxidase and oxidoreductase activities.Conclu-sion SLC22A8 is closely associated with the prognosis of ccRCC and affects its occurrence and development via metabolic disorders,having the potential as the therapeutic target for ccRCC.