CDKN3 alterations in the Kidney renal clear cell carcinoma: prognosis and immunotherapy efficacy

Extensive evidence has unwrapped that Cyclin-dependent kinase inhibitor 3 (CDKN3) is involved in the modulation of many biological processes ranging extracellular matrix (ECM) degradation, invasion, and migration from regulation of immune responses in most malignancies. However, the impact of prognostic value and CDKN3-related immune response on kidney renal clear cell carcinoma (KIRC) remains incompletely transparent. In the current research, we evaluated the prognostic significance and immune-associated mechanism of CDKN3 based on multiple databases and methods, including UCSC, TCGA, GEPIA, CCLE, TIMER, TISIDB, a nd R software. The results demonstrated that CDKN3 was commonly upregulated in 18/33 human cancers, and CDKN3 at high expression was closely correlated with worse clinical outcomes in ACC, LGG, KIRC, KIRP, and UYM based on OS, DFI and PFI survival analysis. More interestingly, CDKN3 expression had a tight correlation with immune function in KIRC by analyzing the role of tumor mutational burden (TMB), immune score, stromal score and immune-related genes, suggesting that CDKN3 may play a vitally important role in the tumor microenvironment (TME). The correlation between immune infiltration and CDKN3 expression in KIRC also validated that CDKN3 expression positively correlated with Macrophage M0, T cells regulatory, CD4 + activated T cells while negatively with Mast cells testing and CD4 + memory T cells. The immune role and function of CDKN3 in KIRC also validated by GSEA analysis, such as Cytokine-cytokine receptor, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, and Chemokine signaling pathway. These findings revealed that CDKN3 correlated with KIRC immunotherapy function. In conclusion, our investigations indicated that CDKN3 might function as an immune-associated biomarker in the development and treatment of KIRC, thereby acting as a promising prognostic and therapeutic target against KIRC.