Exploring gene expression signatures in preeclampsia and identifying hub genes through bioinformatic analysis

IF 3 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta Pub Date : 2025-01-01 DOI:10.1016/j.placenta.2024.12.008

Hamdan Z. Hamdan

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引用次数: 0

Abstract

Introduction

Preeclampsia (PE) is a multisystem disease that affects women during the pregnancy. Its pathogenicity remains unclear, and no definitive screening test can predict its occurrence so far. The aim of this study is to identify the critical genes that are involved in the pathogenicity of PE by applying integrated bioinformatic methods and to investigate the genes' diagnostic capability.

Methods

Datasets that investigated PE have been downloaded from Gene Expression Omnibus (GEO) datasets. Differential gene expression, weighted gene co-expression analysis (WGCNA), protein–protein interaction (PPI) network construction, and finally, the calculation of area under the curve and Receiver operating characteristic curve (ROC) analysis were done for the potential hub genes. The results generated from the GSE186257 dataset (discovery cohort) were validated in the GSE75010 dataset (validation cohort). Following validation of the hub-genes, a multilayer regulatory network was constructed to include the up-stream regulatory elements (transcription factors and miRNAs) of the validated hub-genes.

Results

WGCNA revealed six modules that were significantly correlated with PE. A total of 231 differentially expressed genes (DEGs) were identified. DEGs were intersected with the WGCNA modules' genes, totalling 55 genes. These shared genes were used to construct the PPI network; subsequently, four genes, namely FLT1, HTRA4, LEP and PAPPA2, were identified as hub-genes for PE in the discovery cohort. The expressional of these four hub genes were validated in the validation cohort and found to be highly expressed. ROC analysis in both datasets revealed that all these genes had a significant PE diagnostic ability. The regulatory network showed that FLT1 gene is the most connected and regulated gene among the validated hub-genes.

Discussion

This integrated analysis revealed that FLT1, LEP, HTRA4 and PAPPA2 may be strongly involved in the pathogenicity of PE and act as promising biomarkers and potential therapeutic targets for PE.

查看原文本刊更多论文

通过生物信息学分析探索子痫前期基因表达特征并鉴定中心基因。

子痫前期（PE）是一种多系统疾病，影响妇女在怀孕期间。其致病性尚不清楚，迄今没有明确的筛查试验可以预测其发生。本研究的目的是应用综合生物信息学方法鉴定参与PE致病性的关键基因，并研究这些基因的诊断能力。方法：研究PE的数据集从Gene Expression Omnibus （GEO）数据集下载。对潜在枢纽基因进行差异基因表达、加权基因共表达分析（WGCNA）、蛋白-蛋白相互作用（PPI）网络构建，最后进行曲线下面积计算和Receiver operating characteristic curve （ROC）分析。GSE186257数据集（发现队列）生成的结果在GSE75010数据集（验证队列）中进行验证。在验证中心基因后，构建了一个多层调控网络，包括验证中心基因的上游调控元件（转录因子和mirna）。结果：WGCNA发现6个模块与PE显著相关。共鉴定出231个差异表达基因（DEGs）。deg与WGCNA模块基因相交，共55个基因。这些共享基因被用来构建PPI网络；随后，在发现队列中，FLT1、HTRA4、LEP和PAPPA2四个基因被确定为PE的中心基因。在验证队列中验证了这四个中心基因的表达，发现它们都是高表达的。两个数据集的ROC分析显示，所有这些基因都具有显著的PE诊断能力。调控网络显示，FLT1基因是已验证的中心基因中连接和调控最多的基因。讨论：这项综合分析显示，FLT1、LEP、HTRA4和PAPPA2可能与PE的致病性密切相关，是PE有希望的生物标志物和潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Placenta 医学-发育生物学

CiteScore

6.30

自引率

10.50%

发文量

391

审稿时长

78 days

期刊介绍： Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.