Integrated analysis of the roles and prognostic value of RNA binding proteins in lung adenocarcinoma
Integrated analysis of the roles and prognostic value of RNA binding proteins in lung adenocarcinoma
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DOI：
10.7717/peerj.8509
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发表时间：
2020-02-06
期刊：
影响因子：
2.7
通讯作者：
You, Chongge
中科院分区：
文献类型：
--
作者：
Li, Wei;Li, Na;You, Chongge
肺癌是全球癌症相关死亡的头号原因。RNA结合蛋白(RBPs)的异常表达在多种恶性肿瘤中均有报道，且与肿瘤的发生、发展密切相关。然而，关于RBPs在肺腺癌(LUAD)中的作用还知之甚少。在本研究中，我们从癌症基因组图谱(TCGA)数据库中下载了LUAD的RNA测序数据，并确定了正常组织和肿瘤组织中差异表达的限制性商业惯例。然后，我们进行了一项综合分析，以探索这些限制性商业惯例的表达和预后意义。共鉴定出164个不同表达的限制性商业惯例，其中40个下调，124个上调。途径和基因本体论(GO)分析表明，差异表达的限制性商业惯例主要涉及RNA加工、RNA代谢过程、RNA降解、RNA运输、剪接、定位、翻译调控、RNA结合、转化生长因子-β信号途径、mRNA监控途径和氨基酰-tRNA生物合成。生存分析显示，BOP1、GNL3、WDR12、DCAF13、IGF2BP3或IGF2BP1的高表达与总生存率(OS)低相关。相反，KHDRBS2/SMAD的过度表达预示着这些患者的高OS。ROC曲线分析表明，8个Hub基因对肺腺癌的鉴别诊断具有较好的准确性。这些结果为LUAD的发病机制以及治疗靶点和预后分子标志物的发展提供了新的见解。
Lung cancer is the top cause of carcinoma-associated deaths worldwide. RNA binding proteins (RBPs) dysregulation has been reported in various malignant tumors, and that dysregulation is closely associated with tumorigenesis and tumor progression. However, little is known about the roles of RBPs in lung adenocarcinoma (LUAD). In this study, we downloaded the RNA sequencing data of LUAD from The Cancer Genome Atlas (TCGA) database and determined the differently expressed RBPs between normal and cancer tissues. We then performed an integrative analysis to explore the expression and prognostic significance of these RBPs. A total of 164 differently expressed RBPs were identified, including 40 down-regulated and 124 up-regulated RBPs. Pathway and Gene ontology (GO) analysis indicated that the differently expressed RBPs were mainly related to RNA processing, RNA metabolic process, RNA degradation, RNA transport, splicing, localization, regulation of translation, RNA binding, TGF-beta signaling pathway, mRNA surveillance pathway, and aminoacyl-tRNA biosynthesis. Survival analysis revealed that the high expression of BOP1 or GNL3 or WDR12 or DCAF13 or IGF2BP3 or IGF2BP1 were associated with poor overall survival (OS). Conversely, overexpression of KHDRBS2/SMAD predicted high OS in these patients. ROC curve analysis showed that the eight hub genes with a better diagnostic accuracy to distinguish lung adenocarcinoma. The results provided novel insights into the pathogenesis of LUAD and the development of treatment targets and prognostic molecular markers.