Abstract
Clear cell renal cell carcinoma (ccRCC) is one of the most common renal malignancies worldwide. SLC22A8 plays a key role in renal excretion of organic anions. However, its role in ccRCC remains unclear; therefore, this study aimed to elucidate the relationship between SLC22A8 and ccRCC. The The Cancer Genome Atlas-kidney renal clear cell carcinoma cohort was included in this study. The Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between SLC22A8 expression and clinicopathological characteristics. Multifactorial analysis and Kaplan-Meier survival curves were adopted for correlation between SLC22A8 expression and clinicopathological parameters and overall survival. Utilizing the UALCAN database, the correlation of the expression levels of SLC22A8 DNA methylation in ccRCC was explored. Immunological characterization of SLC22A8 regarding the ccRCC tumor microenvironment was carried out by the single sample Gene Set Enrichment Analysis algorithm and the CIBERSORT algorithm. With the CellMiner database, the analysis of the association between SLC22A8 gene expression and drug sensitivity was further performed. Eventually, gene ontology and Kyoto Encyclopedia of Gene and Genome enrichment analyses were applied to identify the functional and signaling pathways involved in SLC22A8. SLC22A8 expression is associated with age, grade, stage, and tumor status. SLC22A8 protein expression levels, phosphorylated protein levels, and DNA methylation expression levels were lower in ccRCC tissues than in normal tissues, and low methylation levels predicted poor overall survival. Comprehensive analysis of tumor immune infiltration and the tumor microenvironment indicated a higher level of overall immunity in the SLC22A8 low expression group. Gene Enrichment Analysis results showed that low expression of SLC22A8 was associated with immune pathways, such as phagocytosis recognition and humoral immune response. SLC22A8 expression was significantly correlated with survival and immune infiltration in ccRCC and can be used as a prognostic biomarker for ccRCC.