Table_1_Integrated Analysis of the Functions and Prognostic Values of RNA Binding Proteins in Lung Squamous Cell Carcinoma.DOCX

Lung cancer is the leading cause of cancer-related deaths worldwide. Dysregulation of RNA binding proteins (RBPs) has been found in a variety of cancers and is related to oncogenesis and progression. However, the functions of RBPs in lung squamous cell carcinoma (LUSC) remain unclear. In this study, we obtained gene expression data and corresponding clinical information for LUSC from The Cancer Genome Atlas (TCGA) database, identified aberrantly expressed RBPs between tumors and normal tissue, and conducted a series of bioinformatics analyses to explore the expression and prognostic value of these RBPs. A total of 300 aberrantly expressed RBPs were obtained, comprising 59 downregulated and 241 upregulated RBPs. Functional enrichment analysis indicated that the differentially expressed RBPs were mainly associated with mRNA metabolic processes, RNA processing, RNA modification, regulation of translation, the TGF-beta signaling pathway, and the Toll-like receptor signaling pathway. Nine RBP genes (A1CF, EIF2B5, LSM1, LSM7, MBNL2, RSRC1, TRMU, TTF2, and ZCCHC5) were identified as prognosis-associated hub genes by univariate, least absolute shrinkage and selection operator (LASSO), Kaplan–Meier survival, and multivariate Cox regression analyses, and were used to construct the prognostic model. Further analysis demonstrated that high risk scores for patients were significantly related to poor overall survival according to the model. The area under the time-dependent receiver operator characteristic curve of the prognostic model was 0.712 at 3 years and 0.696 at 5 years. We also developed a nomogram based on nine RBP genes, with internal validation in the TCGA cohort, which showed a favorable predictive efficacy for prognosis in LUSC. Our results provide novel insights into the pathogenesis of LUSC. The nine-RBP gene signature showed predictive value for LUSC prognosis, with potential applications in clinical decision-making and individualized treatment.

肺癌是全球范围内癌症相关死亡的首要病因。RNA结合蛋白（RNA binding proteins, RBPs）的表达失调已在多种癌症中被发现，且与肿瘤发生及进展密切相关。然而，RBPs在肺鳞状细胞癌（lung squamous cell carcinoma, LUSC）中的功能仍不明确。本研究从癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库中获取了LUSC的基因表达数据及其对应的临床信息，鉴定出肿瘤组织与正常组织间异常表达的RBPs，并开展了一系列生物信息学分析以探究这些RBPs的表达特征及其预后价值。最终共筛选得到300个异常表达的RBPs，其中59个为下调表达，241个为上调表达。功能富集分析结果显示，差异表达的RBPs主要与mRNA代谢过程、RNA加工、RNA修饰、翻译调控、转化生长因子-β（TGF-β）信号通路以及Toll样受体信号通路密切相关。通过单因素分析、最小绝对收缩和选择算子（least absolute shrinkage and selection operator, LASSO）、Kaplan–Meier生存分析以及多因素Cox回归分析，本研究最终鉴定出9个与预后相关的枢纽RBP基因（A1CF、EIF2B5、LSM1、LSM7、MBNL2、RSRC1、TRMU、TTF2及ZCCHC5），并以此构建了预后预测模型。进一步分析表明，依据该模型计算得到的高风险评分与患者较差的总体生存率显著相关。该预后模型的3年时间依赖性受试者工作特征曲线（time-dependent receiver operator characteristic curve）下面积为0.712，5年时为0.696。本研究还基于这9个RBP基因构建了列线图（nomogram），并在TCGA队列中开展了内部验证，结果显示该列线图对LUSC的预后具有良好的预测效能。本研究结果为LUSC的发病机制提供了全新的视角。这一9个RBP基因的特征标签对LUSC预后具有预测价值，有望在临床决策制定与个体化治疗中得到应用。