Department of NICU, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Sci Rep. 2024 Aug 6;14(1):18215. doi: 10.1038/s41598-024-69065-4.
Polycystic ovary syndrome (PCOS), which is the most prevalent endocrine disorder among women in their reproductive years, is linked to a higher occurrence and severity of atherosclerosis (AS). Nevertheless, the precise manner in which PCOS impacts the cardiovascular well-being of women remains ambiguous. The Gene Expression Omnibus database provided four PCOS datasets and two AS datasets for this study. Through the examination of genes originating from differentially expressed (DEGs) and critical modules utilizing functional enrichment analyses, weighted gene co-expression network (WGCNA), and machine learning algorithm, the research attempted to discover potential diagnostic genes. Additionally, the study investigated immune infiltration and conducted gene set enrichment analysis (GSEA) to examine the potential mechanism of the simultaneous occurrence of PCOS and AS. Two verification datasets and cell experiments were performed to assess biomarkers' reliability. The PCOS group identified 53 genes and AS group identified 175 genes by intersecting DEGs and key modules of WGCNA. Then, 18 genes from two groups were analyzed by machine learning algorithm. Death Associated Protein Kinase 1 (DAPK1) was recognized as an essential gene. Immune infiltration and single-gene GSEA results suggest that DAPK1 is associated with T cell-mediated immune responses. The mRNA expression of DAPK1 was upregulated in ox-LDL stimulated RAW264.7 cells and in granulosa cells. Our research discovered the close association between AS and PCOS, and identified DAPK1 as a crucial diagnostic biomarker for AS in PCOS.
多囊卵巢综合征(PCOS)是育龄妇女中最常见的内分泌疾病之一,与动脉粥样硬化(AS)的发生率和严重程度增加有关。然而,PCOS 影响女性心血管健康的确切方式仍不清楚。本研究利用基因表达综合数据库(GEO)提供的四个 PCOS 数据集和两个 AS 数据集。通过对差异表达基因(DEGs)和关键模块进行功能富集分析、加权基因共表达网络分析(WGCNA)和机器学习算法分析,研究试图发现潜在的诊断基因。此外,本研究还进行了免疫浸润分析和基因集富集分析(GSEA),以研究 PCOS 和 AS 同时发生的潜在机制。通过两个验证数据集和细胞实验评估了生物标志物的可靠性。通过对 DEGs 和 WGCNA 关键模块的交集,PCOS 组鉴定出 53 个基因,AS 组鉴定出 175 个基因。然后,通过机器学习算法分析了两组的 18 个基因。发现凋亡相关蛋白激酶 1(DAPK1)是一个关键基因。免疫浸润和单基因 GSEA 结果表明,DAPK1 与 T 细胞介导的免疫反应有关。在 ox-LDL 刺激的 RAW264.7 细胞和颗粒细胞中,DAPK1 的 mRNA 表达上调。我们的研究发现了 AS 和 PCOS 之间的密切关联,并确定 DAPK1 是 PCOS 中 AS 的一个重要诊断生物标志物。