Identification of novel candidate biomarkers and immune infiltration in polycystic ovary syndrome

• मुख्य लेखकों: Zhijing Na (लेखक), Wen Guo (लेखक), Jiahui Song (लेखक), Di Feng (लेखक), Yuanyuan Fang (लेखक), Da Li (लेखक)
• स्वरूप: पुस्तक
• प्रकाशित: BMC, 2022-07-01T00:00:00Z.
• विषय: article
• ऑनलाइन पहुंच: Connect to this object online.
• Notes: 10.1186/s13048-022-01013-0; 1757-2215
• Keywords: Polycystic ovary syndrome; Biomarkers; Immune infiltration; Machine learning algorithm; CIBERSORT; Gynecology and obstetrics; RG1-991
• Source: Journal of Ovarian Research, Vol 15, Iss 1, Pp 1-13 (2022)

Abstract Background In this study, we aimed to identify novel biomarkers for polycystic ovary syndrome (PCOS) and analyze their potential roles in immune infiltration during PCOS pathogenesis. Methods Five datasets, namely GSE137684, GSE80432, GSE114419, GSE138518, and GSE155489, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were selected from the train datasets. The least absolute shrinkage and selection operator logistic regression model and support vector machine-recursive feature elimination algorithm were combined to screen potential biomarkers. The test datasets validated the expression levels of these biomarkers, and the area under the curve (AUC) was calculated to analyze their diagnostic value. Quantitative real-time PCR was conducted to verify biomarkers' expression in clinical samples. CIBERSORT was used to assess differential immune infiltration, and the correlations of biomarkers with infiltrating immune cells were evaluated. Results Herein, 1265 DEGs were identified between PCOS and control groups. The gene sets related to immune response and adaptive immune response were differentially activated in PCOS. The two diagnostic biomarkers of PCOS identified by us were HD domain containing 3 (HDDC3) and syndecan 2 (SDC2; AUC, 0.918 and 0.816, respectively). The validation of hub biomarkers in clinical samples using RT-qPCR was consistent with bioinformatics results. Immune infiltration analysis indicated that decreased activated mast cells (P = 0.033) and increased eosinophils (P = 0.040) may be a part of the pathogenesis of PCOS. HDDC3 was positively correlated with T regulatory cells (P = 0.0064), activated mast cells (P = 0.014), and monocytes (P = 0.024) but negatively correlated with activated memory CD4 T cells (P = 0.016) in PCOS. In addition, SDC2 was positively correlated with activated mast cells (P = 0.0021), plasma cells (P = 0.0051), and M2 macrophages (P = 0.038) but negatively correlated with eosinophils (P = 0.01) and neutrophils (P = 0.031) in PCOS. Conclusion HDDC3 and SDC2 can serve as candidate biomarkers of PCOS and provide new insights into the molecular mechanisms of immune regulation in PCOS.