Upregulation of SOX9 in the eutopic endometrium of adenomyosis and its association with epithelial-mesenchymal transition

Background: Adenomyosis is an estrogen-dependent benign gynecological disorder, although its exact pathophysiology is still mostly unclear. SRY-box transcription factor 9 (SOX9) is an essential transcription factor regulating epithelial-mesenchymal transition (EMT) in various diseases. This study investigated SOX9 expression in the eutopic endometrium of adenomyosis and its association with the EMT process, providing new insights into the underlying pathological mechanisms. Methods: A retrospective case-control study was conducted, including 60 patients with adenomyosis and 60 control patients with uterine leiomyomas. Eutopic endometrial tissue samples were collected from all participants. The expression levels of SOX9 and key EMT-related markers ((including E-cadherin, N-cadherin, Vimentin, Pan-keratin, and Cytokeratin 7) were evaluated using immunohistochemistry (IHC) and quantitative real-time PCR (RT-qPCR). Furthermore, multivariate logistic regression analysis was performed to assess the association between SOX9 expression and the risk of adenomyosis. Results: Both SOX9 protein levels and mRNA expression were significantly upregulated in the eutopic endometrium of the adenomyosis group compared to the control group (both with P < 0.001). Elevated SOX9 levels positively correlated with the mesenchymal marker Vimentin, and negatively correlated with the epithelial marker E-cadherin. Multivariate analysis indicated that a higher SOX9 score was independently associated with adenomyosis (OR = 1.144, 95% CI 1.008-1.298, P < 0.05). Conclusions: SOX9 is significantly overexpressed in the eutopic endometrium of adenomyosis patients and is closely associated with the EMT process. These findings suggest that SOX9-associated EMT may play a critical role in the pathogenesis of adenomyosis, highlighting SOX9 as a potential biomarker or therapeutic target for this disease.