Comprehensive analysis of the functions and prognostic significance of RNA-binding proteins in bladder urothelial carcinoma.
Comprehensive analysis of the functions and prognostic significance of RNA-binding proteins in bladder urothelial carcinoma.
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DOI：
10.21203/rs.3.rs-44292/v1
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发表时间：
2020-07
影响因子：
2.2
通讯作者：
Changgang Guo;Ting Shao;Dadong Wei;Zhanhua Wang;Mingyang Li;Xiling Jiang;Guochang Bao
中科院分区：
文献类型：
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作者：
Changgang Guo;Ting Shao;Dadong Wei;Zhanhua Wang;Mingyang Li;Xiling Jiang;Guochang Bao
rna结合蛋白（rbp）的改变在各种癌症类型中都有报道；然而，rbp在膀胱尿路上皮癌（BLCA）中的作用尚不清楚。本研究旨在通过生物信息学分析系统地探讨rbp在膀胱癌中的功能和预后意义。从癌症基因组图谱（The Cancer Genome Atlas， TCGA）数据库下载BLCA的RNA测序和临床数据，鉴定正常组织和癌组织之间的差异表达rbp （differential expression rbp, derbp）。共鉴定出388个derbp，包括219个上调rbp和169个下调rbp。筛选所有rbp用于建立预后模型，并将9个rbp （TRIM71、YTHDC1、DARS2、XPOT、ZNF106、FTO、IPO7、EFTUD2和CTU1）视为BLCA中与预后相关的中枢rbp。进一步的分析显示，与基于模型的低风险队列相比，高风险队列的总生存期（OS）更差。训练组的受试者工作特征（ROC）曲线下面积为0.752，试验组的受试者工作特征（ROC）曲线下面积为0.701，说明其预测能力较强。根据9个预后相关rbp建立nomogram，显示BLCA具有较强的预测能力。训练组的c指数为0.7033，测试组的c指数为0.6295。与预后相关的中枢rbp可能参与BLCA的肿瘤发生、发展和转移。本研究结果对揭示BLCA的发病机制，开发新的BLCA治疗靶点和预后分子标志物具有重要意义。
Alterations in RNA-binding proteins (RBPs) are reported in various cancer types; however, the role of RBPs in bladder urothelial cancer (BLCA) remains unknown. This study aimed to systematically examine the function and prognostic significance of RBPs in bladder cancer using bioinformatics analyses. RNA sequencing and clinical data for BLCA were downloaded from The Cancer Genome Atlas (TCGA) database, and differentially expressed RBPs (DERBPs) between normal and cancer tissues were identified. A total of 388 DERBPs were identified, including 219 upregulated and 169 downregulated RBPs. All RBPs were screened for the prognostic model establishment and 9 RBPs (TRIM71, YTHDC1, DARS2, XPOT, ZNF106, FTO, IPO7, EFTUD2, and CTU1) were regarded as prognosis-related hub RBPs in BLCA. Further analysis revealed worse overall survival (OS) in the high-risk cohort compared to the model-based low-risk cohort. The area under the receiver operating characteristic (ROC) curve was 0.752 in the training group and 0.701 in the testing group, which supports the strength of its predictive ability. A nomogram was established according to nine prognosis-related RBPs, which showed strong predictive ability for BLCA. The C-indices of the nomogram were 0.7033 in the training group, and 0.6295 in the testing group. The prognosis-related hub RBPs may be involved in oncogenesis, development, and metastasis of BLCA. Our results will be of great significance in revealing the pathogenesis of BLCA, and developing new therapeutic targets and prognostic molecular markers for BLCA.