基于生物信息学挖掘铜死亡与m6A相关多囊 卵巢综合征关键基因

Identification of Key Genes Associated with Cuproptosis and m6A in Polycystic Ovary Syndrome via Bioinformatics Analysis

摘要: 背景：多囊卵巢综合征(PCOS)是一种常见的生殖内分泌疾病，表现为月经不规律、高雄激素血症和卵巢功能障碍，其相关分子机制尚未完全阐明、病因复杂、高度异质性的临床表现，使得治疗棘手，甚至导致诊断延误或误诊的情况频发。铜死亡(cuproptosis)是一种由铜离子诱导的非凋亡性细胞死亡途径，已被证明在细胞代谢和线粒体功能中发挥关键作用。由于PCOS患者存在线粒体功能异常，铜死亡可能在PCOS的发病机制中扮演重要角色。此外，N6-甲基腺苷(m6A)修饰作为一种关键的表观遗传调控方式，通过调控RNA代谢和基因表达，可能影响PCOS的发生和发展。然而，铜死亡和m6A修饰在PCOS中的作用及其作为诊断标志物的潜力尚未被充分探索。本研究旨在通过生物信息学方法，挖掘与铜死亡和m6A修饰相关的PCOS关键基因，以提供新的诊断标志物。方法：通过整合多个GEO数据集中的基因表达数据，鉴定PCOS患者与对照组之间的差异表达基因(DEGs)，并进一步筛选出与铜死亡相关的差异表达基因(DECuRGs)及m6A修饰靶向的差异表达基因(DEm6ARGs)。通过基因本体(GO)和KEGG通路富集分析，探讨这些基因在PCOS中的潜在生物学功能和通路。同时，进行免疫浸润分析和基因–药物相关性研究，以探索这些关键基因在PCOS中的作用及其治疗潜力。结果：共鉴定出221个DECuRGs和63个DEm6ARGs。富集分析显示，这些基因参与了免疫反应、脂质代谢和细胞凋亡等过程，并可能通过影响线粒体功能和RNA代谢，促进PCOS的发生发展。在PCOS患者中，相关基因的表达水平显著异常。免疫浸润分析揭示了PCOS患者中免疫细胞类型的显著差异，而基因–药物相关性研究表明，这些关键基因可能成为PCOS个性化治疗的新靶点。结论：本研究通过生物信息学方法，鉴定了与铜死亡和m6A修饰相关的PCOS关键基因，揭示了这些基因在PCOS发病机制中的潜在作用。铜死亡和m6A修饰的异常可能通过影响细胞代谢和基因表达，促进PCOS的发生和发展。这些发现为PCOS的早期诊断和个性化治疗提供了新的见解。

Abstract: Background: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by irregular menstruation, hyperandrogenism, and ovarian dysfunction. Its related molecular mechanisms are not fully understood, the etiology is complex, and the clinical manifestations are highly heterogeneous, making treatment difficult and even leading to frequent diagnosis delays or misdiagnosis. Cuproptosis is a non-apoptotic cell death pathway induced by copper ions, which has been shown to play a critical role in cellular metabolism and mitochondrial function. Due to mitochondrial dysfunction in PCOS patients, copper death may play an important role in the pathogenesis of PCOS. In addition, N6 methyladenosine (m6A) modification, as a key epigenetic regulation, may affect the occurrence and development of PCOS by regulating RNA metabolism and gene expression. However, the role of copper death and m6A modification in PCOS and their potential as diagnostic biomarkers have not been fully explored. This study aims to explore key genes related to copper death and m6A modification in PCOS through bioinformatics methods, in order to provide new diagnostic biomarkers. Method: By integrating gene expression data from multiple GEO datasets, differentially expressed genes (DEGs) between PCOS patients and the control group were identified, and further screened for differentially expressed genes associated with copper death (DECuRGs) and m6A modified targeted differentially expressed genes (DEm6ARGs). Explore the potential biological functions and pathways of these genes in PCOS through Gene Ontology (GO) and KEGG pathway enrichment analysis. At the same time, immune infiltration analysis and gene drug correlation studies will be conducted to explore the role and therapeutic potential of these key genes in PCOS. Result: A total of 221 DECuRGs and 63 DEm6ARGs were identified. Enrichment analysis showed that these genes are involved in processes such as immune response, lipid metabolism, and cell apoptosis, and may promote the occurrence and development of PCOS by affecting mitochondrial function and RNA metabolism. In PCOS patients, the expression levels of related genes are significantly abnormal. Immune infiltration analysis revealed significant differences in immune cell types among PCOS patients, while gene drug correlation studies suggest that these key genes may become new targets for personalized treatment of PCOS. Conclusion: This study identified key genes associated with copper death and m6A modification in PCOS through bioinformatics methods, revealing their potential roles in the pathogenesis of PCOS. Copper death and m6A modification abnormalities may promote the occurrence and development of PCOS by affecting cellular metabolism and gene expression. These findings provide new insights for the early diagnosis and personalized treatment of PCOS.