子痫前期新型铜死亡相关预后基因特征。

BACKGROUND: Preeclampsia (PE) is a pregnancy-specific disorder with complex pathogenesis. Cuproptosis is a novel identified form of programmed cell death, however, the link between cuproptosis and clinical outcomes in PE is still not fully understood. In this study, we searched for cuproptosis-related genes (CRGs) in the placental tissues of normal and PE patients to clarify the importance of cuproptosis in the development of PE and provide potential predictive indicators for the occurrence of PE. METHODS: Using RNA sequencing data in the GEO database, we conducted functional enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), supported by linear regression model and operating characteristic curve (ROC) curve analysis, and summarized the role of CRGs in preeclampsia. RESULTS: A total of 2831 differentially expressed genes related to PE were screened through multiple database analyses. After further intersection with 19 reported CRGs, 5 CRGs have been closely associated with the pathogenesis of PE, including NFE2L2, PDHA1, PDHB, DLD and GLS. NFE2L2 was identified as a key central gene. Pearson correlation analysis showed that CRGs could be related to several maternal and fetal outcome factors, including the highest pregnancy blood pressure, placenta weight, umbilical blood flow pulsatility index (PI), and neonatal weight. Linear regression equation revealed that the expression of NFE2L2 is negatively correlated with the highest pregnancy blood pressure and umbilical blood flow PI but positively correlated with placental weight and neonatal weight. QRT-PCR showed that the expression of these CRGs was significantly lower in placental tissues. CONCLUSIONS: This cuproptosis pattern may be a potential prognostic factor in patients with PE and could provide new insights into disease progression.

背景：子痫前期（PE）是一种具有复杂发病机制的妊娠特有疾病。铜死亡是一种新发现的程序性细胞死亡形式，然而，铜死亡与 PE 临床结局之间的联系尚不完全清楚。在本研究中，我们在正常和 PE 患者的胎盘组织中搜索了与铜死亡相关的基因（CRGs），以阐明铜死亡在 PE 发展中的重要性，并为 PE 的发生提供潜在的预测指标。

方法：使用 GEO 数据库中的 RNA 测序数据，我们进行了基因本体论（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）的功能富集分析，支持线性回归模型和工作特征曲线（ROC）曲线分析，并总结了 CRGs 在子痫前期中的作用。

结果：通过多个数据库分析筛选出与 PE 相关的 2831 个差异表达基因。与 19 个报道的 CRGs 进一步交集后，有 5 个 CRGs 与 PE 的发病机制密切相关，包括 NFE2L2、PDHA1、PDHB、DLD 和 GLS。NFE2L2 被确定为关键中心基因。Pearson 相关分析显示，CRGs 可能与几个母婴结局因素有关，包括最高妊娠血压、胎盘重量、脐血流搏动指数（PI）和新生儿体重。线性回归方程显示，NFE2L2 的表达与最高妊娠血压和脐血流 PI 呈负相关，与胎盘重量和新生儿体重呈正相关。实时定量 PCR 显示这些 CRGs 在胎盘组织中的表达明显降低。

结论：这种铜死亡模式可能是 PE 患者的潜在预后因素，并为疾病进展提供新的见解。