Interleukin 20 receptor subunit beta (IL20RB) predicts poor prognosis and regulates immune cell infiltration in clear cell renal cell carcinoma

Abstract

AbstractBackground and objectiveEmerging evidence has proven the robust role of tumor mutation burden (TMB) and immune cell infiltration (ICI) in cancer immunotherapy. However, the precise effect of TMB and ICI on clear cell renal cell carcinoma (ccRCC) remains elusive and merits further investigation. Therefore, we aim to identify the TMB-related genes in predicting prognosis and to explore the potential mechanisms of the identified Interleukin 20 receptor subunit beta (IL20RB) in ICI in ccRCC.MethodThe relative information of patients with ccRCC was obtained from The Cancer Genome Atlas database (TCGA). Immune-related genes were downloaded from the Immunology Database and Analysis Portal database. Cox regression analysis was used to identify prognosis-related immune genes for ccRCC. The relationship ofIL20RBexpression levels with clinicopathological parameters was analyzed using the “limma” and “survival” packages. Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC) databases were used as external validation. Quantitative Real-time PCR (qRT-PCR) and western blots were used to validate the expression levels ofIL20RBin tumor cells. Cell counting kit-8 (CCK-8) assay and colony formation assay were used to examine the effect ofIL20RBon the viability of ccRCC cells. Gene set enrichment analysis (GSEA) was introduced for the analysis ofIL20RB-related signaling pathways. Tumor Immune Estimation Resource (TIMER) and Tumor and Immune System Interaction Database (TISIDB) were utilized to determine the correlation ofIL20RBexpression levels with tumor-infiltrating immune cells (TIICs).ResultsIL20RBwas significantly overexpressed in different ccRCC tissues and cells. HighIL20RBexpression in ccRCC patients was associated with short overall survival, high tumor grade, and advanced TNM stage. After knockdown ofIL20RBwith small interfering RNA (siRNA) technology, ccRCC cells’ proliferation was significantly attenuated. Moreover, overexpression ofIL20RBcould increase the infiltration level of several immune cells, especially T follicular helper cells (Tfh), and overexpressed Tfh cells were correlated with poor prognosis in ccRCC.ConclusionsIL20RBmay function as an immune-associated therapeutic target for it determines cancer progression and regulates immune cell infiltration in ccRCC.