Glypican3 and serglycin as potential biomarkers involved in the pathogenesis of ovarian endometriosis
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This study identified glypican3 and serglycin as potential biomarkers involved in the pathogenesis of ovarian endometriosis.
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Abstract
Endometriosis, a non-malignant gynecological disorder characterized by debilitating symptoms, displays several cancer-like characteristics, including metastatic behavior and extracellular matrix (ECM) remodeling. The dynamics of ECM are largely influenced by proteoglycans (PGs), a family of glycosaminoglycan (GAG)-decorated proteins known for their regulatory impact on cellular behavior through ECM modulation. This study aimed to investigate the dysregulated expression of 20 PG genes in ovarian endometrioma (n = 24) in comparison to eutopic endometrial tissue samples (n = 16) from patients diagnosed with ovarian endometriosis, employing quantitative real-time PCR (qPCR) and immunohistochemistry (IHC). qPCR screening identified four upregulated PG genes-glypican 3 (GPC3), decorin (DCN), serglycin (SRGN), and glypican 5 (GPC5)-whereas 16 PG genes were found to be downregulated. In ovarian endometrioma, relative to eutopic endometrial tissue, GPC3 and SRGN expression were further verified to be significantly overexpressed by 18.6-fold (P < 0.05) and 6.7-fold (P < 0.01), respectively, whereas brevican (BCAN) and syndecan 4 (SDC4) were markedly downregulated by approximately 90 % and 86 %, respectively (both P < 0.001). IHC staining further validated the significant overexpression of GPC3 protein in ovarian endometrioma compared to eutopic and control endometrial tissues (P < 0.0001). In-silico analysis using the Enrichr database identified enriched functional pathways associated with the top overexpressed genes, such as hypoxia, glycolysis, and WNT signaling, known to be implicated in endometriosis. These findings suggest that the overexpression of GPC3 and SRGN may contribute to the pathogenesis of ovarian endometrioma, highlighting their potential as biomarkers and therapeutic targets for this disease.
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