Comprehensive Analysis of Roles of APOBEC3 Gene Family in Clear Cell Renal Cell Carcinoma.

Objectives: The current research focuses on a systematic analysis of the expression patterns of the apolipoprotein B editing complex 3 (APOBEC3) gene family in clear cell renal cell carcinoma (ccRCC) and their impact on disease progression, prognosis, and somatic gene mutations associated with ccRCC.

Methods: A differential expression analysis was performed using the R "limma" package, while a survival analysis was performed using Kaplan-Meier and log-rank tests. A Gene Set Enrichment Analysis performed by the R "clusterProfiler" package compared the high- and low-expression groups. The 10 genes with the highest tumor mutation frequency in the patients with ccRCC were evaluated and presented using the R "maftool" package. The Tumor Immune Estimation Resource (TIMER) algorithm was utilized to predict the immune cell infiltration levels in ccRCC.

Results: All members of the APOBEC3 gene family members were found to be upregulated in ccRCC tumor tissues versus adjacent normal tissues. Higher expressions of APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3D, APOBEC3G, and APOBEC3H were associated with a poorer prognosis for ccRCC. Conversely, higher APOBEC3F expression was associated with a more favorable ccRCC prognosis. Mutation frequencies of genes VHL, PBRM1, TTN, SETD2, and BAP1 genes were higher in the high-expression group of various APOBEC3 compared to the low-expression group. Multiple APOBEC3 gene family (particularly APOBEC3C, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H) also correlated with immune cell infiltration in the ccRCC.

Conclusions: These study findings suggest that APOBEC3 genes are commonly overexpressed in ccRCC, and their expression levels are associated with poor prognosis in ccRCC, somatic gene mutations, cancer immunomodulation, and immune cell infiltration levels in the tumor microenvironment.