The Role of Endoplasmic Reticulum Stress in Polycystic Ovary Syndrome and Exploration of Potential Therapeutic Targets.

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women. In recent years, endoplasmic reticulum (ER) stress has gained increasing attention in the pathogenesis of PCOS. This study aims to explore the potential role of ER stress in PCOS by constructing a predictive model based on ER stress-related genes, and further evaluate the characteristics of immune infiltration and screen potential drugs. Five algorithms, including Lasso, Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Algorithm (XGB), and Generalized Linear Model (GLM), were used to screen key genes associated with PCOS and endoplasmic reticulum (ER) stress. A predictive model was constructed to analyze its diagnostic value in PCOS. External validation of the model was conducted using different datasets to assess its predictive accuracy. Furthermore, immune infiltration analysis was performed to explore the relationship between ER stress-related genes and the immune microenvironment in PCOS, revealing their potential role in disease development through immune response regulation. Finally, molecular docking and drug screening platforms were utilized to identify potential drugs that can modulate the ER stress pathway, providing new drug targets for the clinical treatment of PCOS. Two downregulated genes, NQO1 and NPY, and three upregulated genes, TFEB, JUP, and ATF4, were identified in PCOS cases. The constructed nomogram model demonstrated that the area under the ROC curve for NQO1, TFEB, JUP, NPY, and ATF4 in the validation set were 0.629, 0.600, 0.629, 0.543, and 0.743, respectively, indicating that the PCOS diagnostic model built from these five hub genes has good reliability. Immune infiltration analysis revealed that the expression of the JUP gene was positively correlated with T lymphocyte infiltration, while the expression of TFEB and NPY was negatively correlated with T lymphocyte infiltration, suggesting their potential involvement in immune regulation in PCOS. Through molecular docking and drug screening, 66 potential drugs were identified, 18 of which are already approved for use, providing options for pharmacological treatment of PCOS. The results of this study suggest that endoplasmic reticulum (ER) stress-related genes play an important role in the pathogenesis and development of PCOS, and that accurate predictive models may provide new insights for early diagnosis of the disease. Immune infiltration analysis revealed the potential mechanisms of immune cell involvement in PCOS, while drug screening provides a theoretical basis for future targeted therapies for PCOS.