Bioinformatics and in vitro-based comprehensive analysis of EVI2A expression and its immunological and prognostic significance in Kidney Renal Clear Cell Carcinoma

Abstract

Abstract Background Previous studies have shown that the Ecotropic Viral Integration Site 2A (EVI2A) could serve as a meaningful marker in many diseases, yet its potential biological function and mechanism in kidney renal clear cell (KIRC) carcinoma have not been investigated. Methods TCGA and GEO databases were used for EVI2A gene expression and pan-cancer analysis. We used Kaplan-Meier (K-M) analysis, receiver operating characteristic (ROC) curves, and nomogram to assess the clinical utility of EVI2A. In parallel, we evaluated the immune relevance of the gene by tumor microenvironment (TME), Tumor Immune Single-cell Hub (TISCH), immune checkpoint, and immunotherapy sensitivity analysis. Finally, the expression of this gene was verified in vitro assay and further verified the biological behavior in renal clear cell carcinoma by cell function experiments. Results EVI2A expression in KIRC were upregulated and associated with patients’ tumor grade, T /N/M stage. The diagnostic AUC of EVI2A was 0.906. Its high expression indicated poor overall survival and progression-free survival in KIRC patients. Both GO, and KEGG analysis indicated significant correlations between EVI2A expression and immunity. The higher the EVI2A expression, the higher the TME scores. Furthermore, EVI2A was positively correlated with Tfh cells, CD4 memory T cells and CD8 + T cells. Patients with high expression of EVI2A are more sensitive to PD-1/CTLA-4 and tyrosine kinase inhibitors. In vitro experiments showed that the knockdown of EVI2A reduced KIRC cell proliferation, invasion, and migration. Conclusion Comprehensive analysis indicated that EVI2A may be a potential meaningful biomarker and novel target for KIRC intervention.