Chen Shaorong, Ke Yumin, Chen Weihong, Wu Sijia, Zhuang Xuanxuan, Lin Qiuya, Shi Qirong, Wu Zhuna
Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
Front Mol Biosci. 2023 Aug 10;10:1209144. doi: 10.3389/fmolb.2023.1209144. eCollection 2023.
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. 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. 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 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 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 expression ( < 0.05). 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.
子痫前期（PE）是孕妇的一种严重病症，因此是产科领域的一个重要课题。当前的研究旨在识别PE潜在且重要的免疫相关诊断生物标志物。从基因表达综合数据库（GEO）数据集中，下载了来自PE和血压正常妊娠胎盘样本的三个公共基因表达谱（GSE24129、GSE54618和GSE60438）。在73例PE样本和85例血压正常对照妊娠样本中筛选并确定了差异表达基因（DEG）。这些DEG被用于基因本体论（GO）、京都基因与基因组百科全书（KEGG）、疾病本体论（DO）富集分析以及基因集富集分析（GSEA）。通过最小绝对收缩和选择算子（LASSO）以及支持向量机递归特征消除（SVM - RFE）分析来识别候选生物标志物。应用受试者工作特征曲线（ROC）评估诊断能力。为进一步确认，在GSE75010数据集（80例PE和77例对照）中验证了PE中生物标志物的表达水平和诊断价值，并通过qRT - RCR、蛋白质印迹法和免疫组织化学（IHC）进行了验证。使用CIBERSORT算法计算PE中22种免疫细胞的组成模式。总共识别出15个DEG。GO和KEGG分析表明，这些DEG在类固醇代谢过程、受体配体活性、促性腺激素释放激素分泌以及神经活性配体 - 受体相互作用中富集。识别出的DEG主要与细胞类型良性肿瘤、肾衰竭、不孕症和PE有关。与激素活性、糖基化、多细胞生物体过程以及对骨形态发生蛋白的反应相关的基因集在PE中被激活。该基因被鉴定为PE的诊断生物标志物（AUC = 0.712），并在GSE75010数据集中进一步得到验证（AUC = 0.850）。在临床样本中，该基因的高表达与PE相关。此外，免疫微环境分析表明，γδT细胞、记忆B细胞、M0巨噬细胞和调节性T细胞与该基因的表达呈正相关（P < 0.05）。该基因的表达可被视为PE的诊断生物标志物，并可为未来关于PE发生及分子机制的研究提供新的视角。
