目的：子痫前期（PE）是孕妇中的严重病症，因此在产科中是一个重要的研究课题。本研究旨在识别PE的潜在和显著的与免疫相关的诊断生物标志物。方法：从基因表达数据库（GEO）数据集中，下载了来自PE和正常血压妊娠胎盘样本的三个公共基因表达谱（GSE24129、GSE54618和GSE60438）。从73个PE样本和85个正常血压对照妊娠样本中选择和确定差异表达基因（DEGs）。使用DEGs进行基因本体论（GO）、基因组百科全书（KEGG）、疾病本体论（DO）富集分析和基因集富集分析（GSEA）。通过最小绝对收缩和选择算子（LASSO）和支持向量机递归特征消除（SVM-RFE）分析来确定候选生物标志物。应用受试者工作特征曲线（ROC）评估诊断能力。为了进一步确认，使用GSE75010数据集（80个PE和77个对照）验证PE中生物标志物的表达水平和诊断价值，并通过定量逆转录聚合酶链式反应（qRT-RCR）、Western blot和免疫组织化学（IHC）进行验证。使用CIBERSORT算法计算PE中22种免疫细胞类型的组成模式。结果：总共识别出15个DEGs。GO和KEGG分析显示，DEGs富集于类固醇代谢过程、受体配体活性、GnRH分泌和神经活性配体-受体相互作用。识别到的DEGs主要涉及到细胞类型良性肿瘤、肾功能衰竭、不育和PE。与激素活性、糖基化、多细胞有机体过程和对BMP的反应相关的基因集在PE中被激活。LEP基因被确定为PE的诊断生物标志物（AUC = 0.712），并在GSE75010数据集中得到进一步验证（AUC = 0.850）。LEP的高表达与临床样本中的PE相关。此外，免疫微环境分析表明γδ T细胞、记忆B细胞、M0巨噬细胞和调节性T细胞与LEP表达呈正相关（P < 0.05）。结论：LEP表达可被认为是PE的诊断生物标志物，为进一步研究PE的发生和分子机制提供了新的视角。版权所有 © 2023年陈、柯、陈、吴、庄、林、施和吴。

Objective: Preeclampsia (PE) is a serious condition in pregnant women and hence an important topic in obstetrics. The current research aimed to recognize the potential and significant immune-related diagnostic biomarkers for PE. Methods: From the Gene Expression Omnibus (GEO) data sets, three public gene expression profiles (GSE24129, GSE54618, and GSE60438) from the placental samples of PE and normotensive pregnancy were downloaded. Differentially expressed genes (DEGs) were selected and determined among 73 PE and 85 normotensive control pregnancy samples. The DEGs were used for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). The candidate biomarkers were identified by the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analysis. The receiver operating characteristic curve (ROC) was applied to evaluate diagnostic ability. For further confirmation, the expression levels and diagnostic value of biomarkers in PE were verified in the GSE75010 data set (80 PE and 77 controls) and validated by qRT-RCR, Western blot, and immunohistochemistry (IHC). The CIBERSORT algorithm was used to calculate the compositional patterns of 22 types of immune cells in PE. Results: In total, 15 DEGs were recognized. The GO and KEGG analyses revealed that the DEGs were enriched in the steroid metabolic process, receptor ligand activity, GnRH secretion, and neuroactive ligand-receptor interaction. The recognized DEGs were primarily implicated in cell-type benign neoplasm, kidney failure, infertility, and PE. Gene sets related to hormone activity, glycosylation, multicellular organism process, and response to BMP were activated in PE. The LEP gene was distinguished as a diagnostic biomarker of PE (AUC = 0.712) and further certified in the GSE75010 data set (AUC = 0.850). The high expression of LEP was associated with PE in clinical samples. In addition, the analysis of the immune microenvironment showed that gamma delta T cells, memory B cells, M0 macrophages, and regulatory T cells were positively correlated with LEP expression (P < 0.05). Conclusion: LEP expression can be considered to be a diagnostic biomarker of PE and can offer a novel perspective for future studies regarding the occurrence and molecular mechanisms of PE.Copyright © 2023 Chen, Ke, Chen, Wu, Zhuang, Lin, Shi and Wu.