Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Dec 19, 2020; 10(12): 286-298
Published online Dec 19, 2020. doi: 10.5498/wjp.v10.i12.286
Identification of key genes involved in post-traumatic stress disorder: Evidence from bioinformatics analysis
Li Zeng, Wen-Lin Li, Zheng-Jun Li, Wen Li, Bin Zhang, Li-Li Yang, Yao-Yao Bian
Yao-Yao Bian, School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Li-Li Yang, Li Zeng, School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Li-Li Yang, Wen-Lin Li, Li Zeng, Jingwen Library, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Bin Zhang, Digestive Department, Ningbo Hospital of Traditional Chinese Medicine, Ningbo 315200, Zhejiang Province, China
Wen Li, School of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, Guizhou Province, China
Zheng-Jun Li, Management School, University of St Andrews, St Andrews KY16 9AJ, United Kingdom
Zheng-Jun Li, College of Health Economics Management, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Author contributions: Bian YY, Yang LL, and Zhang B contributed equally to this study; Bian YY and Yang LL designed the study and wrote the manuscript; Zhang B, Li W, and Li ZJ conducted data analysis; Yang LL and Zhang B performed the statistical analysis; Li WL and Zeng L provided several suggestions for manuscript revision.
Supported by the National Natural Science Foundation of China, No. 81603529, 81673982, and 81704084; the Natural Science Foundation of the Jiangsu Higher Education Institutions, No. 16KJB360002; the Advantages of the Nursing Discipline Project of Jiangsu Province, No. 2019YSHL005; China Scholarship Council, No. 201908320373; the Jiangsu Government Scholarship for Overseas Studies; and the Qing Lan Project, No. 014000773/2018-00376.
Institutional review board statement: This study was reviewed and approved by the Animal Experiment Ethics Committee of Nanjing University of Chinese Medicine.
Institutional animal care and use committee statement: All experimental procedures followed the protocols approved by the Institutional Animal Care and Use Committee of Nanjing University of Chinese Medicine.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: Data of the studies are not publicly available but might be shared upon request from the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE guideline, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Li Zeng, MD, PhD, Academic Research, School of First Clinical Medicine, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, Jiangsu Province, China. zengbingli@njucm.edu.cn
Received: February 20, 2020
Peer-review started: February 20, 2020
First decision: September 21, 2020
Revised: October 6, 2020
Accepted: November 4, 2020
Article in press: November 4, 2020
Published online: December 19, 2020
Abstract
BACKGROUND

Post-traumatic stress disorder (PTSD) is a serious stress-related disorder.

AIM

To identify the key genes and pathways to uncover the potential mechanisms of PTSD using bioinformatics methods.

METHODS

Gene expression profiles were obtained from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified by using GEO2R. Gene functional annotation and pathway enrichment were then conducted. The gene-pathway network was constructed with Cytoscape software. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was applied for validation, and text mining by Coremine Medical was used to confirm the connections among genes and pathways.

RESULTS

We identified 973 DEGs including 358 upregulated genes and 615 downregulated genes in PTSD. A group of centrality hub genes and significantly enriched pathways (MAPK, Ras, and ErbB signaling pathways) were identified by using gene functional assignment and enrichment analyses. Six genes (KRAS, EGFR, NFKB1, FGF12, PRKCA, and RAF1) were selected to validate using qRT-PCR. The results of text mining further confirmed the correlation among hub genes and the enriched pathways. It indicated that these altered genes displayed functional roles in PTSD via these pathways, which might serve as key signatures in the pathogenesis of PTSD.

CONCLUSION

The current study identified a panel of candidate genes and important pathways, which might help us deepen our understanding of the underlying mechanism of PTSD at the molecular level. However, further studies are warranted to discover the critical regulatory mechanism of these genes via relevant pathways in PTSD.

Keywords: Post-traumatic stress disorder, Differentially expressed genes, Key pathway, Gene-pathway co-expression, Bioinformatics analysis, Microarray

Core Tip: Post-traumatic stress disorder (PTSD) is an affective disorder after exposure to trauma or stress directly or indirectly. The pathogenesis of PTSD is not entirely understood. The purpose of this study was to uncover the critical signatures and key pathways to elucidate the underlying mechanisms of PTSD at the molecular level. To address this issue, the closely related genes and the most enriched pathways were identified by using bioinformatics analysis, which was then validated by using basic study in an exploratory approach. Our results showed that a series of significantly expressed genes and relevant pathways might serve as potential biomarkers involved in the pathogenesis of PTSD.