RBM39 is a potential prognostic biomarker associated with immune infiltrates in hepatocellular carcinoma

Abstract

Abstract RNA-binding motif protein 39 (RBM39) is a well-studied RNA-binding protein that has been reported to be associated with the process of tumorigenesis and the development of numerous cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to understand the prognostic value of RBM39 in HCC by investigating the relationship between RBM39 expression and clinicopathological features. The cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases were used to analyze the differential expression of RBM39 between normal tissues and that of HCC. Kaplan–Meier and COX regression models were used to analyze the correlation between RBM39 expression and survival rate in the case of HCC. Moreover, gene set enrichment analysis (GSEA) was performed to identify key pathways associated with RBM39. The correlation of RBM39 with tumor immune infiltration was evaluated by single sample gene set enrichment analysis (ssGSEA) using TCGA data. The data generated by bioinformatic approach were further validated using qRT-PCR and immunohistochemistry. The CCK8 and Wound healing assays were performed to investigate the biological function of RBM39 in HCC cells. Our results indicated that there was a significant upregulation of RBM39 in HCC as compared to that of normal tissues. High RBM39 expression was significantly associated with advanced T-stage, histological grade, and pathological stage, and predicted poor overall survival (OS), disease-free survival (DSS), and progression-free interval (PFI) in HCC patients. Multivariate Cox analysis further confirmed that the upregulation of RBM39 expression was an independent prognostic factor for OS in HCC. Moreover, GSEA enrichment analysis indicated that RBM39 was functionally involved in pathways associated with cell cycle, DNA replication, P53, and primary immunodeficiency. RBM39 expression was associated with the infiltrating levels of Th2 cells and DC cells. Knockdown of RBM39 significantly inhibited the proliferation and migration of HCC cells. Altogether, these findings suggest an important role of RBM39 in the development, diagnosis, and prognosis of HCC.