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一种用于子痫前期患者无创诊断的标志性血清生物标志物。

A signature serum biomarker for non-invasive diagnosis of preeclampsia patients.

作者信息

Rashid Teeba Ammar, Farhan Shahd Rajab, Khalaf Aysar Ashour, Sanghvi Gaurav, Uthirapathy Subasini, Jyothi Renuka, Kundlas Mayank, Joshi Kamal Kant, Rudova Anna, Mustafa Yasser Fakri

机构信息

Medical Laboratory Techniques Department, College of Health and Medical Technology, University of Almaarif, Ramadi, Iraq.

Biotechnology Department, College of Applied Science, Fallujah University, Fallujah, Iraq.

出版信息

J Assist Reprod Genet. 2025 Sep 19. doi: 10.1007/s10815-025-03671-7.

Abstract

PURPOSE

This study seeks to identify a non-invasive biomarker for preeclampsia (PE), given its considerable influence on both maternal and fetal health.

METHODS

The identification of differentially expressed genes (DEGs) in PE serum was conducted utilizing GSE192902. Weighted gene co-expression network analysis (WGCNA) was employed to identify functional modules, which were subsequently evaluated for their biological functions. Binary logistic regression was employed to evaluate genes derived from the intersection of DEGs and the most correlated module, with the aim of developing a biomarker model. The analysis of placental gene expression profiles was conducted utilizing GSE234729, and the model underwent validation in GSE149437.

RESULTS

Over 1500 DEGs were identified in the serum of PE patients, with 63% exhibiting downregulation. Co-expression analysis revealed that the expression patterns of PE are structured into 13 distinct modules, with the dark-red module, comprising 55 genes, demonstrating the most significant correlation to the onset of PE. Following this, eight genes from the 26 differentially expressed genes (ADRB1, ARX, C2orf72, FOXB2, HIC1, IRX4, MEX3D, and MIR6724-4) were employed to construct a biomarker model, which attained an area under the curve of 76% (95% CI: 69-83%) in the training cohort and 74% (95% CI: 61-87%) in the validation cohort. Six DEGs were identified from the intersection of results pertaining to serum, placenta, and the dark-red module. However, only two, C2orf72 and RASGEF1C, exhibited consistent downregulation in both placenta and blood.

CONCLUSION

This comprehensive analysis reveals a promising biomarker model that may facilitate early detection of PE.

摘要

目的

鉴于先兆子痫(PE)对母婴健康有重大影响,本研究旨在寻找一种用于先兆子痫的非侵入性生物标志物。

方法

利用GSE192902对PE血清中的差异表达基因(DEG)进行鉴定。采用加权基因共表达网络分析(WGCNA)来识别功能模块,随后对其生物学功能进行评估。采用二元逻辑回归评估来自DEG与最相关模块交集的基因,以建立生物标志物模型。利用GSE234729对胎盘基因表达谱进行分析,并在GSE149437中对该模型进行验证。

结果

在PE患者血清中鉴定出1500多个DEG,其中63%表现为下调。共表达分析显示,PE的表达模式可分为13个不同的模块,其中包含55个基因的暗红色模块与PE的发病表现出最显著的相关性。随后,从26个差异表达基因(ADRB1、ARX、C2orf72、FOXB2、HIC1、IRX4、MEX3D和MIR6724-4)中选取8个基因构建生物标志物模型,该模型在训练队列中的曲线下面积为76%(95%CI:69-83%),在验证队列中的曲线下面积为74%(95%CI:61-87%)。从血清、胎盘和暗红色模块相关结果的交集中鉴定出6个DEG。然而,只有C2orf72和RASGEF1C在胎盘和血液中均表现出一致的下调。

结论

这项综合分析揭示了一个有前景的生物标志物模型,可能有助于PE的早期检测。

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