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基于生物信息学的 lncRNA-miRNA-mRNA 和 TF 调控网络分析揭示食管鳞癌中的功能基因。

Bioinformatics-based analysis of the lncRNA-miRNA-mRNA and TF regulatory networks reveals functional genes in esophageal squamous cell carcinoma.

机构信息

Department of Radiation Oncology, Cancer Hospital of The University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Banshan East road, Gongshu district, Hangzhou, Zhejiang province, China.

Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences.

出版信息

Biosci Rep. 2020 Aug 28;40(8). doi: 10.1042/BSR20201727.

DOI:10.1042/BSR20201727
PMID:32662828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7441485/
Abstract

Esophageal squamous cell carcinoma (ESCC) is a 5-year survival rate unsatisfied malignancies. The study aimed to identify the novel diagnostic and prognostic targets for ESCC. Expression profiling (GSE89102, GSE97051, and GSE59973) data were downloaded from the GEO database. Then, differentially expressed (DE) lncRNAs, DEmiRNAs, and genes (DEGs) with P-values < 0.05, and |log2FC| ≥ 2, were identified using GEO2R. Functional enrichment analysis of miRNA-related mRNAs and lncRNA co-expressed mRNA was performed. LncRNA-miRNA-mRNA, protein-protein interaction of miRNA-related mRNAs and DEGs, co-expression, and transcription factors-hub genes network were constructed. The transcriptional data, the diagnostic and prognostic value of hub genes were estimated with ONCOMINE, receiver operating characteristic (ROC) analyses, and Kaplan-Meier plotter, respectively. Also, the expressions of hub genes were assessed through qPCR and Western blot assays. The CDK1, VEGFA, PRDM10, RUNX1, CDK6, HSP90AA1, MYC, EGR1, and SOX2 used as hub genes. And among them, PRDM10, RUNX1, and CDK6 predicted worse overall survival (OS) in ESCC patients. Our results showed that the hub genes were significantly up-regulated in ESCA primary tumor tissues and cell lines, and exhibited excellent diagnostic efficiency. These results suggest that the hub genes may server as potential targets for the diagnosis and treatment of ESCC.

摘要

食管鳞状细胞癌（ESCC）是一种 5 年生存率不满意的恶性肿瘤。本研究旨在确定 ESCC 的新的诊断和预后靶点。从 GEO 数据库中下载表达谱（GSE89102、GSE97051 和 GSE59973）数据。然后，使用 GEO2R 识别具有 P 值<0.05 和 |log2FC|≥2 的差异表达（DE）lncRNAs、DEmiRNAs 和基因（DEGs）。对 miRNA 相关 mRNAs 和 lncRNA 共表达 mRNA 的功能富集分析进行了分析。构建了 lncRNA-miRNA-mRNA、miRNA 相关 mRNAs 和 DEGs 的蛋白-蛋白相互作用、共表达和转录因子-枢纽基因网络。使用 ONCOMINE、接收者操作特征（ROC）分析和 Kaplan-Meier plotter 分别估计了枢纽基因的转录数据、诊断和预后价值。还通过 qPCR 和 Western blot 分析评估了枢纽基因的表达。CDK1、VEGFA、PRDM10、RUNX1、CDK6、HSP90AA1、MYC、EGR1 和 SOX2 用作枢纽基因。其中，PRDM10、RUNX1 和 CDK6 预测 ESCC 患者的总生存期（OS）更差。我们的结果表明，枢纽基因在 ESCA 原发性肿瘤组织和细胞系中显著上调，并表现出优异的诊断效率。这些结果表明，枢纽基因可能作为 ESCC 诊断和治疗的潜在靶点。

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