Cao Yingyue, Pang Luyi, Jin Shi
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China.
Department of Biomedicine, Southern University of Science and Technology, Shenzhen 518000, China.
Oxid Med Cell Longev. 2022 Nov 28;2022:7654937. doi: 10.1155/2022/7654937. eCollection 2022.
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 cell experiments, and in 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.
RNA结合基序蛋白10(RBM10)是一种剪接因子,据报道它参与多种恶性肿瘤的发生和发展。然而,RBM10在泛癌免疫治疗中的作用尚不清楚。在此,我们利用多个公共数据库首次对RBM10在人类泛癌中的预后价值和免疫功能进行了全面评估。数据显示,大多数肿瘤中RBM10表达异常,其表达与各种癌症的临床预后呈正相关或负相关,这取决于癌症的不同类型和亚型。在大多数肿瘤中,RBM10突变频繁发生,这与肿瘤进展密切相关。此外,我们的结果还表明,RBM10与大多数免疫检查点基因、肿瘤免疫细胞浸润、肿瘤突变负荷和微卫星不稳定性密切相关。此外,RBM10与曲美替尼、17-AAG、PD-0325901、RDEA119、西妥昔单抗和阿法替尼的敏感性显著正相关,表明RBM10抑制剂与这些抗肿瘤药物之间可能存在拮抗作用,并且更有可能产生耐药性。我们还通过细胞实验验证了RBM10的下调增强了肺腺癌细胞的恶性表型,并且在动物实验中表明RBM10的过表达减少了肿瘤的生长。此外,上调RBM10可大大降低PD-L1蛋白水平,而沉默RBM10则可显著提高PD-L1蛋白水平。此外,RBM10的过表达降低了PD-L1的蛋白稳定性。综上所述,我们的泛癌分析表明,RBM10是一种有前景的预后和免疫治疗生物标志物,为癌症免疫治疗提供了新的见解。