-Original-

Identification of a ceRNA Network Driven by Copy Number Variations in Esophageal Cancer

Guoxi Xu, Huaishuai Wang, Yixiang Zhuang, Qiyi Lin, Yinlin Li, Zhicong Cai, Gaofeng Lin and Weibo Liu

Depertment of Gastrointestinal Surgery, Jinjiang Municipal Hospital, Fujian, China

Background: Copy number variation (CNV) is associated with progression of esophageal cancer (EC), a common gastrointestinal neoplasm.
Methods: Using sequencing data, CNV data, and clinical data of EC transcriptome samples obtained from public databases, we performed differential expression analysis on sequencing data. Differentially expressed CNV-driven lncRNAs were screened using the chi-square test, and CNV-driven lncRNA-associated miRNAs and mRNAs were predicted. Cytoscape software was then used to construct ceRNA networks. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to investigate biological functions of mRNAs in the ceRNA network. Survival curves were plotted to explore correlations between lncRNAs in the ceRNA network and overall survival of CNV patients. Multiple databases were used to predict lncRNAs-related drugs.
Results: A dysregulated lncRNA-associated ceRNA network driven by CNV in EC, including 11 lncRNAs, 11 miRNAs and 159 mRNAs, was constructed. Downstream enrichment of mRNAs was related to biological processes such as extracellular matrix organization, indicating that these mRNAs mainly participate in intercellular exchange between tumor cells. Additionally, expression of all lncRNAs in the ceRNA network, except LINC00950, LINC01270 and MIR181A1HG, was correlated with patients' CNV. In addition, none of the 11 lncRNAs was significantly correlated with overall survival of CNV patients. CH5424802 and PD-033299CNV mainly affected the RTK signaling pathway and the cell cycle of tumor cells via RP11-180N14.1 and RP11-273 G15.2 in the ceRNA network.
Conclusions: This study identified 11 CNV-driven lncRNAs that might affect EC development, 2 of which have promising effects if applied to drug treatment. These findings might assist in identifying novel treatments for EC.

J Nippon Med Sch 2023; 90: 426-438

Keywords
esophageal cancer, lncRNA, ceRNA, CNV-driven lncRNA, bioinformatics

Correspondence to
Weibo Liu, Depertment of Gastrointestinal Surgery, Jinjiang Municipal Hospital, No.16, Jinguang Road, Luoshan section, Jinjiang County, Quanzhou, Fujian 362200, China
weiboliuwbl@163.com

Received, October 20, 2022
Accepted, May 1, 2023