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.


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.
Department of Gynecology, Shanghai Changning Maternity and Infant Health Hospital, 773Wuyi Road, Shanghai, 200050, China. shengminhshsh@163.com.
Shengmin
S
Ping
Department of Gynecology, Shanghai Changning Maternity and Infant Health Hospital, 773Wuyi Road, Shanghai, 200050, China.
Chengbin
C
Ma
Department of Gynecology, Shanghai Changning Maternity and Infant Health Hospital, 773Wuyi Road, Shanghai, 200050, China.
Ping
P
Liu
Department of Gynecology, Shanghai Changning Maternity and Infant Health Hospital, 773Wuyi Road, Shanghai, 200050, China.
Longtao
L
Yang
Department of Clinical Laboratory, Shanghai Changning Maternity and Infant Health Hospital, Shanghai, 200050, China.
Xiaoer
X
Yang
Department of Gynecology, Shanghai Changning Maternity and Infant Health Hospital, 773Wuyi Road, Shanghai, 200050, China.
Qiongwei
Q
Wu
Department of Pathology, Shanghai Changning Maternity and Infant Health Hospital, Shanghai, 200050, China.
Xuejun
X
Zhao
Department of Clinical Laboratory, Shanghai Changning Maternity and Infant Health Hospital, Shanghai, 200050, China.
Bo
B
Gong
D002448:Cell Adhesion; D019295:Computational Biology; D015536:Down-Regulation; D004715:Endometriosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D046228:Microarray Analysis; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D015854:Up-Regulation
D014157:Transcription Factors; D053773:Transforming Growth Factor beta1
Endometriosis; Enrichment analysis; Protein–protein interaction network; Transcription factors