ABSTRACT

RBM10 is the RNA-binding protein often absent or mutated in lung adenocarcinoma, rendering it as a potential biomarker or even therapeutic target to prolongate survival time. In this study, we investigated the involvement of RBM10 mutation in the pathogenesis and tumorigenesis of lung adenocarcinoma and identified the differentials in relative signal pathways, aiming to provide the new therapeutic approaches. By performing the systematic TCGA analysis, our results demonstrated that RBM10 mutation was identified in 6% lung adenocarcinoma patients, meanwhile 113 functional genes were identified as significant expression among these patients. Further gene ontology and KEGG analysis were employed to identify the most relative 10 genes and signal pathways. Moreover, four members of the 5-acyl-6, 7-dihydrothiophene [3, 2-c] pyridine (known as “ru-ski”)-ru-ski 43 were identified as the potential drugs for RBM10 mutation lung adenocarcinoma therapy, investigated by the GDSC database. Meanwhile there were 157 genes that were more frequently mutated in the RBM10 mutation group than the wild-type group (p value<0.05). KEGG analysis showed that these genes were enriched in various cancer development pathways and cell proliferation. Finally, our investigations provided the glance at the differential genes and cellular signaling pathways related to RBM10 mutation and identified series of potential drugs for personalized RBM10 mutation lung adenocarcinoma therapy.

摘要

RBM10 是一种 RNA 结合蛋白，在肺腺癌中通常不存在或发生突变，使其成为潜在的生物标志物，甚至是延长生存时间的治疗靶点。在本研究中，我们研究了RBM10突变在肺腺癌发病机制和肿瘤发生中的作用，并确定了相关信号通路的差异，旨在提供新的治疗方法。通过进行系统的 TCGA 分析，我们的结果表明，在 6% 的肺腺癌患者中鉴定出 RBM10 突变，同时鉴定出 113 个功能基因在这些患者中显着表达。进一步的基因本体和KEGG分析被用来识别最相关的10个基因和信号通路。此外，5-acyl-6, 7-dihydrothiophene [3, GDSC 数据库研究了 2-c] 吡啶（称为“ru-ski”）-ru-ski 43 被确定为 RBM10 突变肺腺癌治疗的潜在药物。同时，RBM10 突变组中有 157 个基因突变频率高于野生型组（p值<0.05）。KEGG 分析表明，这些基因在各种癌症发展途径和细胞增殖中富集。最后，我们的研究提供了与 RBM10 突变相关的差异基因和细胞信号通路的概览，并确定了一系列用于个性化 RBM10 突变肺腺癌治疗的潜在药物。