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Updated: Jan 8, 2026
Establishment of an Experimental Mouse Model of Endometrioma to Study its Related Infertility
Published on: April 5, 2024
Bioinformatics Analysis of Hypoxia-Related Mechanisms in Endometriosis: DDR2 as a Potential Diagnostic and
Mingqi Zhao1, Panpan Zhao2, Caiyi Wang1
1Reproductive Hospital of the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Background:
Endometriosis is a chronic gynecological disorder characterized by the presence of endometrial-like tissue outside the uterine cavity, causing chronic pain and infertility. Hypoxia plays a significant role in the progression of endometriosis.
Methods:
We performed bioinformatics analysis on GEO datasets to identify differentially expressed genes (DEGs) in endometriosis, using weighted gene coexpression network analysis (WGCNA)and GeneCards for hypoxia-related genes. Machine learning models identified key hub genes. CCK-8, EdU, and Transwell assays assessed cell proliferation, migration, and invasion. Molecular docking was performed to investigate the interactions between the drug and the protein.
Results:
In the GEO dataset analysis, 2834 DEGs were identified. Using WGCNA, a green module strongly correlated with endometriosis was identified. Intersecting this module with the hypoxia-related genes resulted in the selection of 449 key genes. Machine learning models, including support vector machines (SVMs), were employed to identify hypoxia-related DEGs with significant predictive value. LASSO and SVM-RFE were used to refine this list, ultimately selecting six hub genes: DDR2, ENO3, ESM1, NMBR, PRKAB1, and PRPF19. Validation with an independent dataset confirmed DDR2 as a promising diagnostic biomarker. Functional assays demonstrated that DDR2 knockdown significantly inhibited cell proliferation, migration, and invasion in the endometriosis cell lines VK2/E6E7 and 12Z. DDR2, a receptor tyrosine kinase, mediates extracellular matrix remodeling and cell invasion under hypoxia. By interacting with collagen and HIFs, DDR2 activates pathways that promote MMP secretion, angiogenesis, and migration, facilitating endometriotic cell progression in the hypoxic microenvironment. Molecular docking identified key amino acids near DDR2's binding pocket that form hydrophobic interactions, hydrogen bonds, and π-stacking with baicalein, cavidine, sitogluside, and stigmasterol, further supporting DDR2's potential as a therapeutic target.
Conclusion:
DDR2 is a key hypoxia-related gene in endometriosis and a promising diagnostic and therapeutic biomarker.
