A Potential Autophagy-Related-Gene Based Signature in Patients with Preeclampsia
Jiayu Shen1, Xinyuan Teng1, Jiayao Zhao1
1Department of Obstetrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, 310009 Hangzhou, Zhejiang, China.
Insights
This study identified key autophagy-related genes (ATGs) as potential biomarkers for preeclampsia (PE). A signature of four ATGs demonstrated high diagnostic accuracy in both placental and blood samples, aiding in PE prediction.
Area of Science:
- Genomics and Molecular Biology
- Reproductive Medicine
- Biomarker Discovery
Background:
- Preeclampsia (PE) poses significant risks to maternal and offspring health.
- Identifying reliable diagnostic markers for PE is crucial for timely intervention.
- Autophagy-related genes (ATGs) play roles in various cellular processes relevant to pregnancy complications.
Purpose of the Study:
- To identify potential diagnostic signatures of autophagy-related genes (ATGs) in pregnancies complicated by preeclampsia (PE).
- To explore the role of ATGs in the molecular mechanisms underlying PE development.
Main Methods:
- Analyzed mRNA expression profiles from placental (GSE75010) and blood (GSE48424) samples to identify differentially expressed ATGs in PE.
- Utilized bioinformatics tools including gene ontology, KEGG pathway analysis, and protein-protein interaction networks.
- Employed LASSO logistic regression and SVM-RFE for diagnostic marker screening, with ROC analysis for predictive value assessment.
- Predicted and validated target miRNAs for identified ATGs, constructing a miRNA-mRNA regulatory network.
Main Results:
- Identified 20 differentially expressed ATGs between PE and healthy pregnancies.
- Functional enrichment analysis revealed involvement of ATGs in autophagy, apoptosis, angiogenesis, and inflammatory pathways.
- A signature of four ATGs (LEP, ERO1L, PIK3CB, MAPK8) exhibited excellent diagnostic efficacy in both placenta (AUC=0.869) and blood (AUC=0.914) samples.
- A regulatory network involving 11 miRNAs and the identified ATGs was constructed.
Conclusions:
- An autophagy-related gene signature was established, showing potential for predicting preeclampsia.
- A novel miRNA-mRNA regulatory network was constructed, offering insights into the molecular mechanisms of PE.
- These findings contribute to a deeper understanding of PE pathogenesis and biomarker development.
Objective:
Preeclampsia (PE) is a significant cause of maternal and offspring mortality and morbidity. The purpose of this study is to identify the potential diagnostic signatures of autophagy-related genes (ATGs) in pregnancies with preeclampsia.
Methods:
The expression profile of mRNA was obtained from GSE75010 (placenta samples) and GSE48424 dataset (blood samples). The potential differentially expressed ATGs of PE were screened by R software. The gene-ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, correlation analysis, and protein-protein interactions (PPI) were applied for the differentially expressed ATGs. The diagnostic markers of PE were then screened based on least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE). Receiver operating characteristic (ROC) analysis was used to investigate the predictive value of these diagnostic markers. Target miRNAs were predicted based on the miRDB, DIANA-micro T, Targetscan, and miRWalk databases, and were further validated in GSE84260.
Results:
A total of 20 differentially expressed ATGs were identified between PE and healthy pregnancies. Functional analysis of differentially expressed ATGs indicated several enriched terms related to autophagy, apoptosis, angiogenesis, inflammation, immune response, hypoxia-inducible factor 1 (HIF-1), forkhead box O (FoxO) and AMP-activated protein kinase (AMPK) signaling pathway. A total of 12 ATGs were recognized based on LASSO and SVM-RFE, which made an excellent distinction in both the placenta tissues (area under the curve [AUC] = 0.903) and the blood samples (AUC = 0.972). Furthermore, four feature ATGs (leptin [LEP], ERO1-like [ERO1L], phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [PIK3CB], and mitogen-activated protein kinase 8 [MAPK8]) were screened and also shown an excellent diagnostic efficacy (AUC = 0.869 in placenta samples, and AUC = 0.914 in blood samples). Additionally, 81 target miRNAs were predicted according to the 4 feature ATGs. After evaluating the miRNA expression pattern of GSE84260, 11 miRNAs were selected. Finally, a miRNA-mRNA regulatory network was constructed, which may participate in the development of PE.
Conclusions:
We established an autophagy-related-gene based signature that may predict pregnancies with PE. And we also constructed a miRNA-mRNA regulatory network, which may deepen our understanding of the molecular mechanism underlying the development of PE.
More Related Videos
05:31Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
05:30Trophoblast Cell Recovery from Angiogenesis-Tube Formation Assay for Differentiation Marker Expression Analysis
Published on: November 8, 2024
