Identification of important genes related to ferroptosis in early missed abortion based on WGCNA

Abstract Early missed abortion is defined as a pregnancy of ≤ 12 weeks in which there is a cessation of life in the developing embryo or fetus, leading to its retention within the uterine cavity without being spontaneously expelled promptly. This condition is commonly observed and significantly impa...

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Main Authors: Yulu Zeng, Jiayi Gan, Jinlian Cheng, Changqiang Wei, Xiangyun Zhu, Shisi Wei, Lihong Pang
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-84135-3
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author Yulu Zeng
Jiayi Gan
Jinlian Cheng
Changqiang Wei
Xiangyun Zhu
Shisi Wei
Lihong Pang
author_facet Yulu Zeng
Jiayi Gan
Jinlian Cheng
Changqiang Wei
Xiangyun Zhu
Shisi Wei
Lihong Pang
author_sort Yulu Zeng
collection DOAJ
description Abstract Early missed abortion is defined as a pregnancy of ≤ 12 weeks in which there is a cessation of life in the developing embryo or fetus, leading to its retention within the uterine cavity without being spontaneously expelled promptly. This condition is commonly observed and significantly impacts human reproductive health. This study aimed to identify key genes related to ferroptosis that could serve as novel biomarkers for early missed abortion. Findings from gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicate a correlation between iron- DEFRGS in key modules and the p53 signaling, mitophagy-animal, and protein digestion and absorption pathways. An analysis of the protein-protein interaction (PPI) network was conducted on DEFRGs, identifying five central genes (TP53, EZH2, TIMP1, SLC3A2, and GABARAPL2) using STRING and Cytohubba ROC curves. The expression of pivotal genes in both the missed-abortion and control groups was verified by RT-qPCR. CIBERSORT analysis revealed a notable increase in the infiltration levels of CD8 + T lymphocytes and M2 macrophages among individuals in the early missed abortion group. Additionally, a ceRNA network was constructed to predict interactions between mRNA, miRNA, and lncRNA of the central genes. However, the interacting miRNAs predicted for SLC3A2 in the miRanda, miRDB, and TargetScan databases were limited to hsa-miR-661 and hsa-miR-4311, with no interacting lncRNAs found in the spongeScan database. This research has identified novel genes that could be targeted for the early detection and management of missed abortions.
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spelling doaj-art-7893d6c06bc048969ff4cf0ca53c04572025-01-05T12:15:38ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-024-84135-3Identification of important genes related to ferroptosis in early missed abortion based on WGCNAYulu Zeng0Jiayi Gan1Jinlian Cheng2Changqiang Wei3Xiangyun Zhu4Shisi Wei5Lihong Pang6Department of Prenatal Diagnosis, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Prenatal Diagnosis, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Prenatal Diagnosis, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Prenatal Diagnosis, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Prenatal Diagnosis, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Prenatal Diagnosis, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Prenatal Diagnosis, The First Affiliated Hospital of Guangxi Medical UniversityAbstract Early missed abortion is defined as a pregnancy of ≤ 12 weeks in which there is a cessation of life in the developing embryo or fetus, leading to its retention within the uterine cavity without being spontaneously expelled promptly. This condition is commonly observed and significantly impacts human reproductive health. This study aimed to identify key genes related to ferroptosis that could serve as novel biomarkers for early missed abortion. Findings from gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicate a correlation between iron- DEFRGS in key modules and the p53 signaling, mitophagy-animal, and protein digestion and absorption pathways. An analysis of the protein-protein interaction (PPI) network was conducted on DEFRGs, identifying five central genes (TP53, EZH2, TIMP1, SLC3A2, and GABARAPL2) using STRING and Cytohubba ROC curves. The expression of pivotal genes in both the missed-abortion and control groups was verified by RT-qPCR. CIBERSORT analysis revealed a notable increase in the infiltration levels of CD8 + T lymphocytes and M2 macrophages among individuals in the early missed abortion group. Additionally, a ceRNA network was constructed to predict interactions between mRNA, miRNA, and lncRNA of the central genes. However, the interacting miRNAs predicted for SLC3A2 in the miRanda, miRDB, and TargetScan databases were limited to hsa-miR-661 and hsa-miR-4311, with no interacting lncRNAs found in the spongeScan database. This research has identified novel genes that could be targeted for the early detection and management of missed abortions.https://doi.org/10.1038/s41598-024-84135-3Early missed abortionFerroptosisWGCNAImmune cell infiltration
spellingShingle Yulu Zeng
Jiayi Gan
Jinlian Cheng
Changqiang Wei
Xiangyun Zhu
Shisi Wei
Lihong Pang
Identification of important genes related to ferroptosis in early missed abortion based on WGCNA
Scientific Reports
Early missed abortion
Ferroptosis
WGCNA
Immune cell infiltration
title Identification of important genes related to ferroptosis in early missed abortion based on WGCNA
title_full Identification of important genes related to ferroptosis in early missed abortion based on WGCNA
title_fullStr Identification of important genes related to ferroptosis in early missed abortion based on WGCNA
title_full_unstemmed Identification of important genes related to ferroptosis in early missed abortion based on WGCNA
title_short Identification of important genes related to ferroptosis in early missed abortion based on WGCNA
title_sort identification of important genes related to ferroptosis in early missed abortion based on wgcna
topic Early missed abortion
Ferroptosis
WGCNA
Immune cell infiltration
url https://doi.org/10.1038/s41598-024-84135-3
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