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

Abstract

RNA binding motif protein 10 (RBM10) is a splicing factor that has been reported to be involved in the occurrence and progression of multiple malignancies. However, the RBM10 involvement in pan-cancer immunotherapy is not clear. In here, we provide the first comprehensive assessment of the prognostic value and immunological function of RBM10 in human pan-cancer utilizing multiple public databases. Data reveal the aberrant RBM10 expression in most tumors, and its expression is positively or negatively linked with the clinical prognosis of various cancers, depending on the different types and subtypes of cancers. In most tumors, RBM10 mutations are frequently occurred, which is closely related to tumor progression. Moreover, our results also show that RBM10 is considerably linked with most of the immune checkpoint genes, tumor immune cell infiltration, tumor mutation burden, and microsatellite instability. Additionally, RBM10 is significantly positively correlated with the sensitivity of trametinib, 17-AAG, PD-0325901, RDEA119, cetuximab, and afatinib, indicating potential antagonism between RBM10 inhibitors and these antitumor drugs, and more likely to develop drug resistance. We also verify that downregulation of RBM10 enhances the malignant phenotype of lung adenocarcinoma cells using in vitro cell experiments, and in vivo animal experiments show that the overexpression of RBM10 reduces the growth of tumors. Furthermore, upregulating RBM10 greatly reduces the PD-L1 protein levels, while silencing RBM10 considerably enhances PD-L1 protein levels. Moreover, the overexpression of RBM10 decreases the protein stability of PD-L1. To sum up, our pan-cancer analysis indicates that RBM10 is a promising biomarker for prognosis and immunotherapy, which provides a new insight for cancer immunotherapy.