Heidarzadehpilehrood Roozbeh, Pirhoushiaran Maryam, Osman Malina Binti, Ling King-Hwa, Hamid Habibah Abdul
Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran 1417613151, Iran.
Arch Med Res. 2025 Apr;56(3):103129. doi: 10.1016/j.arcmed.2024.103129. Epub 2024 Dec 7.
Polycystic ovary syndrome (PCOS) is an endocrine and reproductive condition affecting women of reproductive age, although its expression profiles and molecular pathways are not fully understood.
To identify the transcriptome expression profiles of peripheral blood mononuclear cells (PBMCs) in women with PCOS and controls. To investigate noninvasive diagnostic biomarkers and potential treatment targets to improve women's fertility.
RNA sequencing (RNA-Seq) was conducted on PBMC samples from six patients with PCOS and six healthy controls. qRT-PCR validation was carried out in 68 subjects. Multivariate logistic regression was performed to assess the combined impact of biomarkers.
A total of 186 differentially expressed genes (DEG) were found between patients and controls (logFC >1, p <0.05). Enrichment analysis revealed cytokine-mediated signaling pathways, cytokine activity, and cytokine-cytokine receptor interaction. RNA sequencing showed consistency with qRT-PCR. Women with PCOS had significantly higher levels of AQP9 (p <0.001), PROK2 (p = 0.001), and S100A12 (p <0.001) expression compared to controls. AQP9 (AUC = 0.77), PROK2 (AUC = 0.71), and S100A12 (AUC = 0.82) adequately discriminated women with PCOS from healthy controls. In addition, multiple logistic regression on biomarkers resulted in a significant diagnostic power with an AUC = 0.89, 95% CI: 0.81-0.97, p <0.0001. Further associations were analyzed between relative gene expression and clinical, anthropometric, hormonal, and ultrasonographic data.
Dysregulated RNA expression in PBMCs may contribute to an increased risk of PCOS and serve as a potential diagnostic biomarker. The involvement of inflammatory and cytokine-related pathways supports the notion that PCOS is a chronic inflammatory condition.
多囊卵巢综合征（PCOS）是一种影响育龄女性的内分泌和生殖疾病，尽管其表达谱和分子途径尚未完全明确。
确定PCOS女性和对照者外周血单个核细胞（PBMCs）的转录组表达谱。研究无创诊断生物标志物和潜在治疗靶点，以改善女性生育能力。
对6例PCOS患者和6例健康对照者的PBMC样本进行RNA测序（RNA-Seq）。在68名受试者中进行qRT-PCR验证。进行多因素逻辑回归分析以评估生物标志物的综合影响。
患者与对照者之间共发现186个差异表达基因（DEG）（logFC>1，p<0.05）。富集分析揭示了细胞因子介导的信号通路、细胞因子活性以及细胞因子-细胞因子受体相互作用。RNA测序结果与qRT-PCR一致。与对照组相比，PCOS女性的AQP9（p<0.001）、PROK2（p=0.001）和S100A12（p<0.001）表达水平显著更高。AQP9（AUC=0.77）、PROK2（AUC=0.71）和S100A12（AUC=0.82）能够充分区分PCOS女性与健康对照者。此外，对生物标志物进行多因素逻辑回归分析，得到了显著的诊断效能，AUC=0.89，95%CI：0.81-0.97，p<0.0001。进一步分析了相对基因表达与临床、人体测量、激素和超声数据之间的关联。
PBMCs中RNA表达失调可能导致PCOS风险增加，并可作为潜在的诊断生物标志物。炎症和细胞因子相关途径的参与支持了PCOS是一种慢性炎症性疾病的观点。
