A 16 Epithelia-Mesenchymal Transition Associated LncRNAs Signature to Optimize Prognosis Predication of Stomach Adenocarcinoma

Yanhua Yan, Xinru He, Yanfen Chen, Yuancheng Huang, Xiaotao Jiang, Junhui Zheng, Xinfa Chen
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Abstract

The study aimed to identifying critical long non-coding RNAs (lncRNAs) and constructed a prognostic signature to optimize prognosis predication of patients with Stomach Adenocarcinoma (STAD). STAD is a common malignant tumor with high metastasis rate and low survival rate. LncRNAs participate in the regulation process of epithelial-mesenchymal transition (EMT) and development of STAD. RNAseq data was obtained from TCGA-STAD, while 200 EMT-associated genes (EAGs) from ‘HALLMARK_EPITHELIAL_MESENCHYMA-L _TRANSITION’ gene set. Differentially expressed EAGs and EMT-associated lncRNAs (EALs) were identified. Moreover, Lasso Cox regression analysis was used to construct a signature of differentially expressed EALs, and univariate and multivariate analyses, Kaplan-Meier analysis, receiver operating characteristic curve (ROC) analysis and nomogram were conducted to predict its prognostic value. Enrichment functional analysis was performed. Quantitative Real-Time PCR (qRT-PCR) was used to determine lncRNAs expressions in cell lines. A total of 52 differentially expressed EAGs and 320 EALs were identified in this study. Meanwhile, 16 EALs was used to construct the signature, and further analysis indicated that it had high prognostic value for STAD patients. Enrichment functional analysis revealed the signature was correlated to tumor immunity in STAD. Moreover, three novel EALs expressions were confirmed in cell lines. A novel survival signature was established to predict and evaluate prognosis of STAD patients.
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16个上皮-间质转化相关lncrna标记优化胃腺癌预后预测
本研究旨在鉴定关键的长非编码RNA(lncRNA),并构建预后标志,以优化胃腺癌(STAD)患者的预后预测。STAD是一种常见的恶性肿瘤,转移率高,生存率低。lncRNA参与上皮-间充质转化(EMT)的调节过程和STAD的发展。RNAseq数据来自TCGA-STAD,而200个EMT相关基因(EAG)来自“HALLMARK_ETHELIAL_MESENCHYMA-L _TRANSITION”基因集。鉴定了差异表达的EAG和EMT相关的lncRNA(EAL)。此外,Lasso-Cox回归分析用于构建差异表达EAL的特征,并进行单变量和多变量分析、Kaplan-Meier分析、受试者操作特征曲线(ROC)分析和列线图来预测其预后价值。进行了富集功能分析。定量实时PCR(qRT-PCR)用于测定细胞系中lncRNA的表达。本研究共鉴定出52个差异表达的EAG和320个EAL。同时,使用16个EAL构建签名,进一步分析表明它对STAD患者具有较高的预后价值。富集功能分析显示,STAD的特征与肿瘤免疫相关。此外,在细胞系中证实了三种新的EAL表达。建立了一种新的生存特征来预测和评估STAD患者的预后。
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