Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jan 15, 2020; 12(1): 54-65
Published online Jan 15, 2020. doi: 10.4251/wjgo.v12.i1.54
Identification of candidate biomarkers correlated with pathogenesis of postoperative peritoneal adhesion by using microarray analysis
Yao-Yao Bian, Li-Li Yang, Yan Yan, Min Zhao, Yan-Qi Chen, Ya-Qi Zhou, Zi-Xin Wang, Wen-Lin Li, Li Zeng
Yao-Yao Bian, Ya-Qi Zhou, Zi-Xin Wang, School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Li-Li Yang, Min Zhao, Yan-Qi Chen, 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
Yan Yan, Guang′anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
Author contributions: Bian YY, Yang LL, and Yan Y contributed equally to this study; Bian YY conceived and designed the study, made the data acquisition, and prepared the manuscript with Yang LL; Yan Y and Zhao M conducted the data analysis; Chen YQ, Zhou YQ, and Wang ZX contributed to the animal experiment; Li WL and Zeng L provided several suggestions for manuscript revision.
Supported by the National Natural Science Foundation of China, No. 81704084, No. 81603529, and No. 81673982; the Science and Technology Projects of Jiangsu Provincial Bureau of Traditional Chinese Medicine, No. YB2017002 and No. YB2015002; the Natural Science Foundation of the Jiangsu Higher Education Institutions, No. 16KJB360002; the Postgraduate Research and Practice Innovation Program of Jiangsu Province, No. KYCX18_1541; the Qing Lan Project; and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine (ZYX03KF63), Jiangsu Government Scholarship for Overseas Studies and China Scholarship Council.
Institutional animal care and use committee statement: The protocol was approved by the Laboratory Animal Management Committee of the Nanjing University of Chinese Medicine.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose.
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:
Corresponding author: Li Zeng, PhD, Professor, School of First Clinical Medicine and Jingwen Library, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, Jiangsu Province, China.
Received: June 4, 2019
Peer-review started: June 4, 2019
First decision: July 31, 2019
Revised: August 5, 2019
Accepted: September 12, 2019
Article in press: September 12, 2019
Published online: January 15, 2020
Research background

Postoperative peritoneal adhesion (PPA), characterized with abdominal pain, female infertility, and even bowel obstruction after surgery, has always been a major concern. The occurrence and formation of adhesion are from complex biological processes. However, the molecular mechanisms of the basis of microarray data profile, followed by PPA formation, are largely unknown.

Research motivation

The occurrence and development of PPA is a complex biological process, during which many genes and pathways are involved in the pathogenesis of adhesion formation. As such, we developed microarray analysis combined with experimental methods to understand the underlying mechanisms of PPA at the transcriptomic and molecular levels.

Research objectives

The aim of this study was to uncover the molecular mechanisms of PPA formation after surgery using bioinformatics analysis, and to validate the results using rodent adhesion models.

Research methods

The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis. A panel of key altered genes and related pathways involved in adhesion formation were identified using bioinformatics analysis methods. And the microarray results were verified by performing quantitative PCR and western blotting in vivo preliminarily.

Research results

In total, 446 expressed genes were altered in peritoneal adhesion. We found that several hub genes (e.g., TNF, IL-1β, IL-6, CXCL1, CXCL2) were marked as significant biomarkers associated with PPA. Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway. According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies, TLR4, MyD88, and NF-κB played essential roles in Toll-like signaling transduction. Here, we gained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of PPA. The results of the microarray analysis were consistent with the animal experiments.

Research conclusions

Our findings provide initial evidence about the regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion in the pathogenesis of PPA. Future studies are required to validate the results.

Research perspectives

These findings may extend our understanding of the molecular mechanisms of PPA. Further functional and gene knockout studies are warranted to elucidate the exact effects on the transcriptional expression of genes regulated by NF-κB axis activation.