Integrated Bioinformatics Analysis and Validation of the Prognostic Value of RBM10 Expression in Hepatocellular Carcinoma

Abstract

Background RBM10ʹ s function in hepatocellular carcinoma (HCC) has rarely been addressed. We intend to explore the prognostic significance and therapeutic meaning of RBM10 in HCC in this study. Methods Multiple common databases were integrated to analyze the expression status and prognostic meaning of RBM10 in HCC. The relationship between RBM10 mRNA level and clinical features was also assessed. Multiple enrichment analyses of the differentially expressed genes between RBM10 high- and low- transcription groups were constructed by using R software (version 4.0.2). A Search Tool for Retrieval of Interacting Genes database was used to construct the protein–protein interaction network between RBM10 and other proteins. A tumor immune estimation resource database was employed to identify the relationship between RBM10 expression and immune cell infiltrates. The prognostic value of RBM10 expression was validated in our HCC cohort by immunohistochemistry test. Results The transcription of RBM10 mRNA was positively correlated with tumor histologic grade (p < 0.001), T classification (p < 0.001), and tumor stage (p < 0.001). High transcription of RBM10 in HCC predicted a dismal overall survival (p = 0.0037) and recurrence-free survival (p < 0.001). Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene Set Enrichment Analysis all revealed that RBM10 was involved in the regulation of cell cycle, DNA replication, and immune-related pathways. Tumor immune estimation analysis revealed that RBM10 transcription was positively related to multiple immune cell infiltrates and the expressions of PD-1 and PD-L1 . Conclusion RBM10 was demonstrated to be a dismal prognostic factor and a potential biomarker for immune therapy in HCC in that it may be involved in the immune-related signaling pathways.

RBM10 Is a Biomarker Associated with Pan-Cancer Prognosis and Immune Infiltration: System Analysis Combined with In Vitro and Vivo Experiments

“…In this study, we found that the RBM10 expression was negatively correlated with B cells, CD8+ T cells, neutrophils, macrophages, and DC cell infiltration levels in most tumor types, indicating that RBM10 was likely to affect tumor development and prognosis by impacting the tumor microenvironment. It is worth noting that in HCC, RBM10 was significantly positively correlated with a variety of immune cells, which was consistent with the results of Pang et al [8]. In addition, we further found that the RBM10 expression was closely related to tumor-associated macrophages (TAMs) in a variety of cancers through xCell.…”

“…Previously, the correlation of the RBM10 expression with tumor stages was reported to be negative in pancreatic cancer [25]. The correlation of high expression of RBM10 in HCC with more advanced tumor stages was significantly positive [8]. Additionally, our prognostic analysis indicated that in certain malignancies, the high RBM10 expression was a risk factor and was considerably linked to the poorer OS, PFS, and RFS.…”

“…Atsumi et al [35] found that RBM10 regulated the activity of NF-κB promoters through selective splicing of DNMT3B, thus regulating the development of inflammation. A bioinformatics study found that in HCC, the RBM10 expression was positively correlated with infiltration of CD8 + T cell, as well as the expression of PD-1 and PD-L1 [8]. However, a recent report showed that CD8+ T cells showed a higher level of infiltration in LUAD with RBM10 deletion [16].…”

“…It is first discovered in 1995 [6] and is mainly responsible for the splicing of precursor mRNA and posttranscriptional regulation [7]. The roles of RBM10 in regulating apoptosis, cell proliferation, metastasis, and other biological activities have been proved [6,8]. Upregulation of RBM10 inhibits the growth of primary chondrocytes by inducing apoptosis and blocking cell migration as well as inducing apoptosis by reducing the Bcl-2 expression [9].…”

“…As we all known, immunotherapy and targeted therapy have greatly improved the prognosis of cancer patients. The study by Pang et al [8] have shown that the high RBM10 expression is positively linked with most immune cell infiltrates and the expressions of PD-1 and PD-L1 in hepatocellular carcinoma (HCC). In addition, a recent research confirms that the low RBM10 expression significantly increases the immune activity of LUAD and is negatively linked with CD8+ T cells having a tumorsuppressive effect, which makes it evident that RBM10 is linked with immune infiltration [16].…”