Unveiling the molecular mechanisms of recurrent miscarriage through endoplasmic reticulum stress related gene expression

Abstract Recurrent miscarriage (RM) is a reproductive disorder affecting couples worldwide. The underlying molecular mechanisms remain elusive, even though emerging evidence has implicated endoplasmic reticulum stress (ERS). We investigated RM- and ERS-related genes to develop a diagnostic model tha...

Full description

Saved in:
Bibliographic Details
Main Authors: Xiaodan Yin, Wei Yang, Mingwei Xin, Qian Han, Siqi Guan, Junqin He
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-024-77642-w
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1841544793113493504
author Xiaodan Yin
Wei Yang
Mingwei Xin
Qian Han
Siqi Guan
Junqin He
author_facet Xiaodan Yin
Wei Yang
Mingwei Xin
Qian Han
Siqi Guan
Junqin He
author_sort Xiaodan Yin
collection DOAJ
description Abstract Recurrent miscarriage (RM) is a reproductive disorder affecting couples worldwide. The underlying molecular mechanisms remain elusive, even though emerging evidence has implicated endoplasmic reticulum stress (ERS). We investigated RM- and ERS-related genes to develop a diagnostic model that can enhance predictive ability. We utilized the R package GEO query to extract and process Gene Expression Omnibus data, applying batch correction, normalization, and differential gene expression analysis with limma. ERS-related differentially expressed genes (ERSRGs) were identified through Gene Ontology and Kyoto Encyclopedia of genes and genomes analyses, and their diagnostic potential was assessed. Diagnostic models were developed using logistic regression, support vector machines, and least absolute shrinkage and selection operators, complemented by immune infiltration analysis and regulatory network construction. Integrated analysis revealed 1395 differentially expressed genes (DEGs), including 626 upregulated and 769 downregulated genes. Seventeen ERSRGs were identified. KEAP1 and YIPF5 displayed high diagnostic accuracy (area under the curve [AUC] > 0.9). Gene Ontology and Kyoto Encyclopedia of genes and genomes analyses highlighted the role of ESRDEGs in cellular responses to ERS, protein processing, and apoptosis. Diagnostic models demonstrated robust predictive performance (AUC > 0.9). A molecular interaction was found between RM and the ERS response, and the identified ESRDEGs could serve as potential biomarkers for diagnosis.
format Article
id doaj-art-04e0543a554f4c5f873cd3cd2f0e431a
institution Kabale University
issn 2045-2322
language English
publishDate 2025-01-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-04e0543a554f4c5f873cd3cd2f0e431a2025-01-12T12:14:27ZengNature PortfolioScientific Reports2045-23222025-01-0115111910.1038/s41598-024-77642-wUnveiling the molecular mechanisms of recurrent miscarriage through endoplasmic reticulum stress related gene expressionXiaodan Yin0Wei Yang1Mingwei Xin2Qian Han3Siqi Guan4Junqin He5Department of TCM, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of TCM, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of TCM, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of TCM, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of TCM, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalDepartment of TCM, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care HospitalAbstract Recurrent miscarriage (RM) is a reproductive disorder affecting couples worldwide. The underlying molecular mechanisms remain elusive, even though emerging evidence has implicated endoplasmic reticulum stress (ERS). We investigated RM- and ERS-related genes to develop a diagnostic model that can enhance predictive ability. We utilized the R package GEO query to extract and process Gene Expression Omnibus data, applying batch correction, normalization, and differential gene expression analysis with limma. ERS-related differentially expressed genes (ERSRGs) were identified through Gene Ontology and Kyoto Encyclopedia of genes and genomes analyses, and their diagnostic potential was assessed. Diagnostic models were developed using logistic regression, support vector machines, and least absolute shrinkage and selection operators, complemented by immune infiltration analysis and regulatory network construction. Integrated analysis revealed 1395 differentially expressed genes (DEGs), including 626 upregulated and 769 downregulated genes. Seventeen ERSRGs were identified. KEAP1 and YIPF5 displayed high diagnostic accuracy (area under the curve [AUC] > 0.9). Gene Ontology and Kyoto Encyclopedia of genes and genomes analyses highlighted the role of ESRDEGs in cellular responses to ERS, protein processing, and apoptosis. Diagnostic models demonstrated robust predictive performance (AUC > 0.9). A molecular interaction was found between RM and the ERS response, and the identified ESRDEGs could serve as potential biomarkers for diagnosis.https://doi.org/10.1038/s41598-024-77642-wRecurrent miscarriageEndoplasmic reticulum stressDiagnostic modelImmune InfiltrationBioinformatics
spellingShingle Xiaodan Yin
Wei Yang
Mingwei Xin
Qian Han
Siqi Guan
Junqin He
Unveiling the molecular mechanisms of recurrent miscarriage through endoplasmic reticulum stress related gene expression
Scientific Reports
Recurrent miscarriage
Endoplasmic reticulum stress
Diagnostic model
Immune Infiltration
Bioinformatics
title Unveiling the molecular mechanisms of recurrent miscarriage through endoplasmic reticulum stress related gene expression
title_full Unveiling the molecular mechanisms of recurrent miscarriage through endoplasmic reticulum stress related gene expression
title_fullStr Unveiling the molecular mechanisms of recurrent miscarriage through endoplasmic reticulum stress related gene expression
title_full_unstemmed Unveiling the molecular mechanisms of recurrent miscarriage through endoplasmic reticulum stress related gene expression
title_short Unveiling the molecular mechanisms of recurrent miscarriage through endoplasmic reticulum stress related gene expression
title_sort unveiling the molecular mechanisms of recurrent miscarriage through endoplasmic reticulum stress related gene expression
topic Recurrent miscarriage
Endoplasmic reticulum stress
Diagnostic model
Immune Infiltration
Bioinformatics
url https://doi.org/10.1038/s41598-024-77642-w
work_keys_str_mv AT xiaodanyin unveilingthemolecularmechanismsofrecurrentmiscarriagethroughendoplasmicreticulumstressrelatedgeneexpression
AT weiyang unveilingthemolecularmechanismsofrecurrentmiscarriagethroughendoplasmicreticulumstressrelatedgeneexpression
AT mingweixin unveilingthemolecularmechanismsofrecurrentmiscarriagethroughendoplasmicreticulumstressrelatedgeneexpression
AT qianhan unveilingthemolecularmechanismsofrecurrentmiscarriagethroughendoplasmicreticulumstressrelatedgeneexpression
AT siqiguan unveilingthemolecularmechanismsofrecurrentmiscarriagethroughendoplasmicreticulumstressrelatedgeneexpression
AT junqinhe unveilingthemolecularmechanismsofrecurrentmiscarriagethroughendoplasmicreticulumstressrelatedgeneexpression