Molecular mechanisms underlying endometriosis pathogenesis revealed by bioinformatics analysis of microarray data

Objective To identify differentially expressed genes (DEGs) in endometriosis and further analyze molecular mechanisms implicated in disease pathogenesis. Materials and methods Gene expression data (ID: GSE7846) of human endometrial endothelial cells (HEECs) collected from eutopic endometria tissue o...

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Bibliographic Details
Published in:Archives of gynecology and obstetrics 2016-04, Vol.293 (4), p.797-804
Main Authors: Ping, Shengmin, Ma, Chengbin, Liu, Ping, Yang, Longtao, Yang, Xiaoer, Wu, Qiongwei, Zhao, Xuejun, Gong, Bo
Format: Article
Language:English
Subjects:
Cell Adhesion
Computational Biology
Down-Regulation
Endocrinology
Endometriosis
Endometriosis - genetics
Endometriosis - pathology
Female
Gene expression
Gene Expression Profiling
Gene Regulatory Networks
General Gynecology
Gynecology
Human Genetics
Humans
Medicine
Medicine & Public Health
Microarray Analysis
Obstetrics/Perinatology/Midwifery
Pathogenesis
Signal Transduction
Transcription Factors - genetics
Transcription Factors - metabolism
Transforming Growth Factor beta1 - genetics
Up-Regulation
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Summary:Objective To identify differentially expressed genes (DEGs) in endometriosis and further analyze molecular mechanisms implicated in disease pathogenesis. Materials and methods Gene expression data (ID: GSE7846) of human endometrial endothelial cells (HEECs) collected from eutopic endometria tissue of patients with and without endometriosis were downloaded from Gene Expression Omnibus. DEGs were screened using Limma package, followed by enrichment analysis using clusterProfiler package in R. Thereafter, protein–protein interactions (PPIs) were analyzed using STRING (Search Tool for the Retrieval of Interacting Genes) database and visualized by Cytoscape software. Meanwhile, transcription factors were screened from the DEGs based on TRANSFA database, followed by construction of regulatory network using Cytoscape. Results A total of 2255 up- and 408 down-regulated genes were identified in endometriosis patients as compared with control patients. Those DEGs were predominantly enriched in focal adhesion (e.g., FN1 , EGF , FYN , EGFR , RAC1 , CCND1 and JUN ), regulation of actin cytoskeleton (e.g., FN1 , EGF , EGFR , RAC1 and JUN ) and MAPK signaling pathway (e.g., EGF , EGFR , RAC1 , JUN , TGFB1 and MYC ). Importantly, EGF , EGFR , JUN , FN1 , RAC1 , TGFB1 , CCND1 and FYN were hub nodes in the PPI network. Additionally, TGFB1 , SMAD1 and SMAD4 showed up-regulation in TGFB signaling pathway. Transcription factor MYC had a regulatory effect on the most DEGs, including TGFB1 , RAC1 and CCND1 . Conclusions Focal adhesion, regulation of actin cytoskeleton, MAPK and TGFB / SMAD signaling pathway may be important molecular mechanism underlying the pathogenesis of endometriosis.
ISSN:0932-0067
1432-0711
DOI:10.1007/s00404-015-3875-y