Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2019; 25(48): 6890-6901
Published online Dec 28, 2019. doi: 10.3748/wjg.v25.i48.6890
Comprehensive multi-omics analysis identified core molecular processes in esophageal cancer and revealed GNGT2 as a potential prognostic marker
Guo-Min Liu, Xuan Ji, Tian-Cheng Lu, Li-Wei Duan, Wen-Yuan Jia, Yun Liu, Mao-Lei Sun, Yun-Gang Luo
Guo-Min Liu, Xuan Ji, Wen-Yuan Jia, Yun Liu, Mao-Lei Sun, Yun-Gang Luo, Jilin Provincial Medicine Anti-Tumor Engineering Center, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
Guo-Min Liu, Wen-Yuan Jia, Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
Xuan Ji, Yun Liu, Mao-Lei Sun, Yun-Gang Luo, Department of Stomatology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
Tian-Cheng Lu, Life Sciences College, Jilin Agricultural University, Changchun 130118, Jilin Province, China
Li-Wei Duan, Department of Gastroenterology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
Author contributions: Liu GM and Ji X designed the research; Lu TC and Duan LW performed the research; Jia WY and Liu Y analyzed the data; Sun ML and Luo YG wrote the paper.
Supported by Construction of Engineering Laboratory of Jilin Development and Reform Commission (grant no. 3J115AK93429) and Jilin Provincial Science and Technology Department Medical Health Project (grant no. 3D5195001429).
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Second Hospital of Jilin University.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Yun-Gang Luo, MD, Attending Doctor, Department of Stomatology, Jilin Provincial Medicine Anti-Tumor Engineering Center, The Second Hospital of Jilin University, No. 218, Ziqiang Street, Changchun 130041, Jilin Province, China. luoygjlu@sina.com
Received: September 29, 2019
Peer-review started: September 29, 2019
First decision: November 27, 2019
Revised: December 3, 2019
Accepted: December 14, 2019
Article in press: December 14, 2019
Published online: December 28, 2019
Abstract
BACKGROUND

Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world. Although a series of studies on esophageal cancer have been reported, the molecular pathogenesis of the disease remains elusive.

AIM

To investigate comprehensively the molecular process of esophageal cancer.

METHODS

Differential expression analysis was performed to identify differentially expressed genes (DEGs) in different stages of esophageal cancer from The Cancer Genome Atlas data. Exacting gene interaction modules were generated, and hub genes in the module interaction network were found. Further, through survival analysis, methylation analysis, pivot analysis, and enrichment analysis, some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer.

RESULTS

A total of 7457 DEGs and 14 gene interaction modules were identified. These module genes were significantly involved in the positive regulation of protein transport, gastric acid secretion, insulin-like growth factor receptor binding, and other biological processes as well as p53 signaling pathway, epidermal growth factor signaling pathway, and epidermal growth factor receptor signaling pathway. Transcription factors (including hypoxia inducible factor 1A) and non-coding RNAs (including colorectal differentially expressed and hsa-miR-330-3p) that significantly regulate dysfunction modules were identified. Survival analysis showed that G protein subunit gamma transducin 2 (GNGT2) was closely related to survival of esophageal cancer. DEGs with strong methylation regulation ability were identified, including SST and SH3GL2. Furthermore, the expression of GNGT2 was evaluated by quantitative real time polymerase chain reaction, and the results showed that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines. Moreover, cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines.

CONCLUSION

This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.

Keywords: Esophageal cancer, Molecular pathogenesis, Enrichment analysis, Gene interaction module, Regulatory factors, GNGT2

Core tip: Based on the esophageal cancer-associated RNA-seq in The Cancer Genome Atlas, we studied differentially expressed genes of esophageal cancer at various stages, constructed a protein-protein interaction network, obtained 14 dysfunctional modules, and screened Hub genes. We performed enrichment analysis to predict non-coding RNA and transcription factors as well as methylation analysis of the genes in the module. A series of regulatory factors was predicted to regulate to a certain degree the potential dysfunction mechanism of esophageal cancer, which provides new insight for future studies of esophageal cancer.