Integrated pan-cancer analysis reveals the immunological and prognostic potential of RBFOX2 in human tumors

Abstract

BackgroundThe role of RNA-binding fox one homolog 2 (RBFOX2) in the progression of multiple tumors is increasingly supported by evidence. However, the unclearness pertaining to the expression of RBFOX2, its prognostic potential, and its correlation with the tumor microenvironment (TME) in pan-cancer persists. This study aims to comprehensively investigate the immunological prognostic value of RBFOX2.MethodsThe Cancer Genome Atlas Gene Expression Omnibus Genotype-Tissue Expression (GTEx), TIMER2.0, Kaplan-Meier (K–M) Plotter, University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), cbioportal, and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) were utilized for a systematic analysis of RBFOX2. This analysis included studying its expression, prognostic value, DNA methylation, enrichment analysis, immune infiltration cells, and immune-related genes. Additionally, qRT-PCR, CCK-8, colony formation, transwell assays, and immunohistochemistry were employed to analyze the expression and biological function of RBFOX2 in liver cancer.ResultsVariations in RBFOX2 expression have been observed across diverse tumors and have been identified as indicators of unfavorable prognosis. It is closely linked to immune infiltration cells, immune checkpoints, chemokines, and chemokine receptors in the TME. Higher levels of RBFOX2 have been significantly associated with low response and poor prognosis in patients with non-small cell lung cancer (NSCLC) and melanoma who receive immunotherapy. Furthermore, the DNA methylation of RBFOX2 varies across different types of cancer and has shown better prognosis in patients with BLCA, BRCA, CESC, COAD, DLBC, HNSC, LAML, LGG, LUAD, PAAD, SKCM and THYM. Interestingly, RBFOX2 expression was found to be lower in hepatocellular carcinoma (HCC) patients’ tumor tissues compared to their paired adjacent tissues. In vitro studies have shown that knockdown of RBFOX2 significantly promotes the growth and metastasis of liver cancer cells.ConclusionThis study investigates the correlation between DNA methylation, prognostic value, and immune cell infiltration with the expression of RBFOX2 in pan-cancer and indicates its potential role to inhibit metastasis of liver cancer.