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RNA 结合蛋白在头颈部鳞状细胞癌中的作用及预后价值的综合分析。

Comprehensive Analysis of the Roles and Prognostic Value of RNA-Binding Proteins in Head and Neck Squamous Cell Carcinoma.

机构信息

Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.

Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, P.R. China.

出版信息

DNA Cell Biol. 2020 Oct;39(10):1789-1798. doi: 10.1089/dna.2020.5641. Epub 2020 Jul 23.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a malignancy with relatively high incidence and poor prognosis. RNA-binding proteins (RBPs) were reported to be dysregulated in multiple cancers and were closely associated with tumor initiation and progression. However, an integrated analysis of the roles of RBPs in HNSCC has not been conducted. In the present study, we obtained transcriptome data and corresponding clinical information of HNSCC patients from The Cancer Genome Atlas database and screened out differentially expressed RBPs between tumor and normal tissues. Subsequently, we utilized a series of bioinformatics analyses to elucidate the potential functions and prognostic value of these RBPs in HNSCC. As a result, a total of 88 aberrantly expressed RBPs were identified, including 63 downregulated and 25 upregulated RBPs. Functional enrichment analysis suggested that the differentially expressed RBPs mainly participated in mRNA metabolic processes, RNA processing, RNA transport, regulation of RNA stability, RNA degradation, and mRNA surveillance pathway. Three RBP genes (, , and ) were determined as prognosis-related hub genes from which and were selected to construct a prognostic signature based on LASSO Cox regression algorithm. Further analysis demonstrated that the high-risk patient group stratified by the risk signature has advanced tumor grade and poorer overall survival when compared with low-risk group. Moreover, univariate analysis showed that the risk score, tumor stage, T stage, and N stage were significantly associated with patient overall survival and the multivariate analysis results indicated that the risk score and age were greatly correlated with patient prognosis. Overall, this study provided a comprehensive landscape of RBPs in HNSCC and identified an effective gene signature for predicting the clinical outcomes of HNSCC patient, which may contribute to clinical decision making and individualized cancer treatment.

摘要

头颈部鳞状细胞癌(HNSCC)是一种发病率相对较高、预后较差的恶性肿瘤。有报道称,RNA 结合蛋白(RBPs)在多种癌症中失调,与肿瘤的发生和进展密切相关。然而,目前尚未对 RBPs 在 HNSCC 中的作用进行综合分析。本研究从癌症基因组图谱数据库中获取 HNSCC 患者的转录组数据和相应的临床信息,筛选出肿瘤组织与正常组织之间差异表达的 RBPs。随后,我们利用一系列生物信息学分析来阐明这些 RBPs 在 HNSCC 中的潜在功能和预后价值。结果共鉴定出 88 个异常表达的 RBPs,其中包括 63 个下调的 RBPs 和 25 个上调的 RBPs。功能富集分析表明,差异表达的 RBPs 主要参与了 mRNA 代谢过程、RNA 加工、RNA 转运、RNA 稳定性调节、RNA 降解和 mRNA 监测途径。从这些差异表达的 RBPs 中筛选出 3 个与预后相关的 hub 基因(、和),并基于 LASSO Cox 回归算法构建了一个预后签名。进一步分析表明,根据风险签名分层的高风险患者组与低风险组相比,肿瘤分级更高,总体生存率更差。此外,单因素分析表明,风险评分、肿瘤分期、T 分期和 N 分期与患者总体生存率显著相关,多因素分析结果表明,风险评分和年龄与患者预后密切相关。总之,本研究提供了 HNSCC 中 RBPs 的全面图谱,并鉴定了一个有效的基因签名,用于预测 HNSCC 患者的临床结局,这可能有助于临床决策和个体化癌症治疗。

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