Li Junqing, Zhou Wenjie, Wei Jitao, Xiao Xing, An Tailai, Wu Wenhui, He Yulong
Digestive Disease Center, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518000, People's Republic of China.
Department of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
Onco Targets Ther. 2021 Mar 4;14:1689-1705. doi: 10.2147/OTT.S297973. eCollection 2021.
To investigate the prognostic value and biological function of RNA binding proteins (RBPs) in stomach adenocarcinoma (STAD).
Datasets of the differentially expressed genes (DEGs) were downloaded from the TCGA-based (The Cancer Genome Atlas) GEPIA database, from which the differentially expressed RBPs were determined. Functions and prognostic values of these determined RBPs were systematically investigated by a series of methods in bioinformatics analysis. In addition, transwell assays were performed to explore the effect of in STAD cells.
Three hundred and sixty-two differentially expressed RBPs were determined, with 331 up-regulated and 31 down-regulated. Seven RBPs () were identified to be prognosis-related and adopted to construct a prognostic model. Compared with low-risk patients in TCGA training cohort, TCGA testing cohort and GEO cohort, high-risk patients had poorer overall survival (OS). The area under the ROC curves of this prognostic model were 0.804, 0.644 and 0.581 for TCGA training cohort, TCGA testing cohort and GEO cohort, respectively, justifying itself as a good prognostic model with reliable predictive ability. Using the seven identified RBPs, we then constructed a nomogram to generate a clinical utility model. The regulatory networks and functions of the seven RBPs were then investigated, the results of which demonstrated that and reduced the number of infiltrated immune cells. In-vitro experiments showed that the downregulation of PTBP1 weakened the migration and invasion capability of AGS and HGC27 cells.
The seven-gene signature can be used as a reliable STAD prognostic biomarker, and these findings help us better understand the prognostic roles and functions of RBPs in STAD.
探讨RNA结合蛋白（RBPs）在胃腺癌（STAD）中的预后价值及生物学功能。
从基于癌症基因组图谱（TCGA）的GEPIA数据库下载差异表达基因（DEGs）数据集，从中确定差异表达的RBPs。通过一系列生物信息学分析方法系统研究这些确定的RBPs的功能和预后价值。此外，进行Transwell实验以探究其在STAD细胞中的作用。
确定了362个差异表达的RBPs，其中331个上调，31个下调。鉴定出7个RBPs与预后相关，并用于构建预后模型。与TCGA训练队列、TCGA测试队列和GEO队列中的低风险患者相比，高风险患者的总生存期（OS）较差。该预后模型在TCGA训练队列、TCGA测试队列和GEO队列中的ROC曲线下面积分别为0.804、0.644和0.581，证明其是一个具有可靠预测能力的良好预后模型。利用鉴定出的7个RBPs，构建了列线图以生成临床实用模型。随后研究了这7个RBPs的调控网络和功能，结果表明其减少了浸润免疫细胞的数量。体外实验表明，PTBP1的下调减弱了AGS和HGC27细胞的迁移和侵袭能力。
七基因特征可作为可靠的STAD预后生物标志物，这些发现有助于我们更好地理解RBPs在STAD中的预后作用和功能。
