Yan Zhang, Xiujuan Chen, Yuan Lin, Xiaoqing Liu, Xiumei Xiong
{"title":"结合生物信息学分析鉴定多囊卵巢综合征内质网应激相关的关键途径和基因。","authors":"Yan Zhang, Xiujuan Chen, Yuan Lin, Xiaoqing Liu, Xiumei Xiong","doi":"10.3389/fmolb.2024.1504015","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic condition impacting millions of women worldwide. This study sought to identify granulosa cell endoplasmic reticulum stress (GCERS)-related differentially expressed genes (DEGs) between women with PCOS and those without PCOS using bioinformatics and to investigate the related molecular mechanisms.</p><p><strong>Methods: </strong>Two datasets were downloaded from GEO and analysed using the limma package to identify DEGs in two groups-PCOS and normal granulosa cells. Enrichment analyses, including GO, KEGG, and GSEA, were then conducted on the DEGs. Differential immune infiltration was assessed using CIBERSORT and correlations with immune cell biomarkers were evaluated. Networks for protein-protein interactions, transcription factor-target genes, miRNA-target genes, and drug-target genes were constructed and visualized using Cytoscape to identify key hub gene nodes. Finally, key genes were analysed for differential expression and correlated.</p><p><strong>Results: </strong>Overall, 127 co-DEGs were identified in the two datasets. Our study revealed that these DEGs were primarily associated with cell cycle arrest, p53-mediated signal transduction, drug response, and gland development, with molecular functions enriched in growth factor binding, collagen binding, and receptor protein kinase activity. GSEA revealed that the co-DEGs were primarily associated with immune and inflammatory pathways. Eleven hub genes-<i>MMP9</i>, <i>SPI1</i>, <i>IGF2R</i>, <i>GPBAR1</i>, <i>PDGFA</i>, <i>BMPR1A</i>, <i>LIFR</i>, <i>PRKAA1</i>, <i>MSH2</i>, <i>CDC25C</i>, and <i>KCNH2</i>-were identified through the PPI, TF target genes, miRNA target genes, and drug target gene networks.</p><p><strong>Conclusion: </strong>We identified several crucial genes and pathways linked to the onset and development of PCOS. Our findings offer a clear connection between PCOS and GCERS, clarify the molecular mechanisms driving PCOS progression, and offer new perspectives for discovering valuable therapeutic targets and potential biomarkers for the condition.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1504015"},"PeriodicalIF":3.9000,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754070/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identification of crucial pathways and genes linked to endoplasmic reticulum stress in PCOS through combined bioinformatic analysis.\",\"authors\":\"Yan Zhang, Xiujuan Chen, Yuan Lin, Xiaoqing Liu, Xiumei Xiong\",\"doi\":\"10.3389/fmolb.2024.1504015\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic condition impacting millions of women worldwide. This study sought to identify granulosa cell endoplasmic reticulum stress (GCERS)-related differentially expressed genes (DEGs) between women with PCOS and those without PCOS using bioinformatics and to investigate the related molecular mechanisms.</p><p><strong>Methods: </strong>Two datasets were downloaded from GEO and analysed using the limma package to identify DEGs in two groups-PCOS and normal granulosa cells. Enrichment analyses, including GO, KEGG, and GSEA, were then conducted on the DEGs. Differential immune infiltration was assessed using CIBERSORT and correlations with immune cell biomarkers were evaluated. Networks for protein-protein interactions, transcription factor-target genes, miRNA-target genes, and drug-target genes were constructed and visualized using Cytoscape to identify key hub gene nodes. Finally, key genes were analysed for differential expression and correlated.</p><p><strong>Results: </strong>Overall, 127 co-DEGs were identified in the two datasets. Our study revealed that these DEGs were primarily associated with cell cycle arrest, p53-mediated signal transduction, drug response, and gland development, with molecular functions enriched in growth factor binding, collagen binding, and receptor protein kinase activity. GSEA revealed that the co-DEGs were primarily associated with immune and inflammatory pathways. Eleven hub genes-<i>MMP9</i>, <i>SPI1</i>, <i>IGF2R</i>, <i>GPBAR1</i>, <i>PDGFA</i>, <i>BMPR1A</i>, <i>LIFR</i>, <i>PRKAA1</i>, <i>MSH2</i>, <i>CDC25C</i>, and <i>KCNH2</i>-were identified through the PPI, TF target genes, miRNA target genes, and drug target gene networks.</p><p><strong>Conclusion: </strong>We identified several crucial genes and pathways linked to the onset and development of PCOS. Our findings offer a clear connection between PCOS and GCERS, clarify the molecular mechanisms driving PCOS progression, and offer new perspectives for discovering valuable therapeutic targets and potential biomarkers for the condition.</p>\",\"PeriodicalId\":12465,\"journal\":{\"name\":\"Frontiers in Molecular Biosciences\",\"volume\":\"11 \",\"pages\":\"1504015\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-01-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754070/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Molecular Biosciences\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3389/fmolb.2024.1504015\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Molecular Biosciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmolb.2024.1504015","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Identification of crucial pathways and genes linked to endoplasmic reticulum stress in PCOS through combined bioinformatic analysis.
Background: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic condition impacting millions of women worldwide. This study sought to identify granulosa cell endoplasmic reticulum stress (GCERS)-related differentially expressed genes (DEGs) between women with PCOS and those without PCOS using bioinformatics and to investigate the related molecular mechanisms.
Methods: Two datasets were downloaded from GEO and analysed using the limma package to identify DEGs in two groups-PCOS and normal granulosa cells. Enrichment analyses, including GO, KEGG, and GSEA, were then conducted on the DEGs. Differential immune infiltration was assessed using CIBERSORT and correlations with immune cell biomarkers were evaluated. Networks for protein-protein interactions, transcription factor-target genes, miRNA-target genes, and drug-target genes were constructed and visualized using Cytoscape to identify key hub gene nodes. Finally, key genes were analysed for differential expression and correlated.
Results: Overall, 127 co-DEGs were identified in the two datasets. Our study revealed that these DEGs were primarily associated with cell cycle arrest, p53-mediated signal transduction, drug response, and gland development, with molecular functions enriched in growth factor binding, collagen binding, and receptor protein kinase activity. GSEA revealed that the co-DEGs were primarily associated with immune and inflammatory pathways. Eleven hub genes-MMP9, SPI1, IGF2R, GPBAR1, PDGFA, BMPR1A, LIFR, PRKAA1, MSH2, CDC25C, and KCNH2-were identified through the PPI, TF target genes, miRNA target genes, and drug target gene networks.
Conclusion: We identified several crucial genes and pathways linked to the onset and development of PCOS. Our findings offer a clear connection between PCOS and GCERS, clarify the molecular mechanisms driving PCOS progression, and offer new perspectives for discovering valuable therapeutic targets and potential biomarkers for the condition.
期刊介绍：
Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology.
Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life.
In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.
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