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通过生物信息学分析和实验验证鉴定子痫前期发病机制中的关键基因。

Identification of key genes in the pathogenesis of preeclampsia via bioinformatic analysis and experimental verification.

机构信息

Department of Basic Medical Research, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Key Laboratory of Cardiovascular Diseases, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.

The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan City People's Hospital, Qingyuan, Guangdong, China.

出版信息

Front Endocrinol (Lausanne). 2023 Jul 28;14:1190012. doi: 10.3389/fendo.2023.1190012. eCollection 2023.

Abstract

BACKGROUND

Preeclampsia (PE) is the primary cause of perinatal maternal-fetal mortality and morbidity. The exact molecular mechanisms of PE pathogenesis are largely unknown. This study aims to identify the hub genes in PE and explore their potential molecular regulatory network.

METHODS

We downloaded the GSE148241, GSE190971, GSE74341, and GSE114691 datasets for the placenta and performed a differential expression analysis to identify hub genes. We performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO), Gene Set Enrichment Analysis (GSEA), and Protein-Protein Interaction (PPI) Analysis to determine functional roles and regulatory networks of differentially expressed genes (DEGs). We then verified the DEGs at transcriptional and translational levels by analyzing the GSE44711 and GSE177049 datasets and our clinical samples, respectively.

RESULTS

We identified 60 DEGs in the discovery phase, consisting of 7 downregulated genes and 53 upregulated genes. We then identified seven hub genes using Cytoscape software. In the verification phase, 4 and 3 of the seven genes exhibited the same variation patterns at the transcriptional level in the GSE44711 and GSE177049 datasets, respectively. Validation of our clinical samples showed that CADM3 has the best discriminative performance for predicting PE.

CONCLUSION

These findings may enhance the understanding of PE and provide new insight into identifying potential therapeutic targets for PE.

摘要

背景

子痫前期(PE)是围产期母婴死亡和发病的主要原因。PE 发病的确切分子机制在很大程度上尚不清楚。本研究旨在鉴定 PE 中的枢纽基因,并探讨其潜在的分子调控网络。

方法

我们下载了 GSE148241、GSE190971、GSE74341 和 GSE114691 数据集进行胎盘差异表达分析,以鉴定枢纽基因。我们进行了基因本体论(GO)、京都基因与基因组百科全书(KEGG)、疾病本体论(DO)、基因集富集分析(GSEA)和蛋白质-蛋白质相互作用(PPI)分析,以确定差异表达基因(DEGs)的功能作用和调控网络。然后,我们通过分析 GSE44711 和 GSE177049 数据集以及我们的临床样本,分别在转录和翻译水平验证了 DEGs。

结果

我们在发现阶段鉴定了 60 个 DEGs,包括 7 个下调基因和 53 个上调基因。然后,我们使用 Cytoscape 软件鉴定了 7 个枢纽基因。在验证阶段,在 GSE44711 和 GSE177049 数据集中,7 个基因中的 4 个和 3 个在转录水平上表现出相同的变化模式。对我们的临床样本的验证表明,CADM3 对预测 PE 具有最佳的判别性能。

结论

这些发现可能有助于提高对 PE 的认识,并为确定 PE 的潜在治疗靶点提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/10420078/3d9ce438b024/fendo-14-1190012-g001.jpg

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