Yuan Ma, Chunfang Ha, Ruyue Li, Ruiqi Zhang, Min Li
{"title":"解读子宫内膜异位症内质网应激和免疫浸润的分子串扰","authors":"Yuan Ma, Chunfang Ha, Ruyue Li, Ruiqi Zhang, Min Li","doi":"10.1111/aji.70092","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Endometriosis (EMs), characterized by ectopic endometrial growth causing infertility. Endoplasmic reticulum stress (ERS) is an important cellular defense mechanism. However, the correlation between ERS and EMs remains unclear. We aimed to investigate the relationship between them, identify biomarkers, and offer new insights into the treatment of EMs.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Two RNA expression datasets (GSE120103 and GSE25628) related to EMs in <i>Homo sapiens</i> were used to identify ERS-differentially expressed genes (ERS-DEGs). Protein–protein interaction (PPI) networks and CytoHubba (Cytoscape) identified ERS-associated HUB genes, with receiver operating characteristic curves (ROC) evaluating diagnostic value. Constructed mRNA-microRNA (miRNA)/RNA-transcription factor (TF) interaction networks and performed ssGSEA to compare immune infiltration between EMs patients and controls. Real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC) were performed to assess potential biomarker levels.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Thirty-three ERS-DEGs were identified, with nine HUB genes (<i>HSPA5, XBP1, HSP90B1, DNAJC3, PDIA3, PDIA6, PDIA4, HERPUD1</i>, and <i>MANF</i>) demonstrating diagnostic efficacy (AUC > 0.7). Furthermore, immune infiltration revealed a significant relationship between immune cell abundance and HUB gene expression. Experimental validation confirmed the consistency of four biomarkers (<i>HSPA5, HSP90B1, PDIA6</i>, and <i>HERPUD1</i>). Regulatory network analysis identified 62 miRNAs and 44 TFs interacting with HUB genes, suggesting a multifactorial immunometabolic axis.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>We identified four biomarkers (<i>HSPA5, HSP90B1, PDIA6</i>, and <i>HERPUD1</i>) associated with ERS that offer new insights into the detection and treatment of EMs. Our findings indicate an abnormal response to ERS and immune system infiltration contribute to the progression of EMs.</p>\n </section>\n </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 5","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70092","citationCount":"0","resultStr":"{\"title\":\"Deciphering the Molecular Crosstalk of Endoplasmic Reticulum Stress and Immune Infiltration in Endometriosis\",\"authors\":\"Yuan Ma, Chunfang Ha, Ruyue Li, Ruiqi Zhang, Min Li\",\"doi\":\"10.1111/aji.70092\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Endometriosis (EMs), characterized by ectopic endometrial growth causing infertility. Endoplasmic reticulum stress (ERS) is an important cellular defense mechanism. However, the correlation between ERS and EMs remains unclear. We aimed to investigate the relationship between them, identify biomarkers, and offer new insights into the treatment of EMs.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Two RNA expression datasets (GSE120103 and GSE25628) related to EMs in <i>Homo sapiens</i> were used to identify ERS-differentially expressed genes (ERS-DEGs). Protein–protein interaction (PPI) networks and CytoHubba (Cytoscape) identified ERS-associated HUB genes, with receiver operating characteristic curves (ROC) evaluating diagnostic value. Constructed mRNA-microRNA (miRNA)/RNA-transcription factor (TF) interaction networks and performed ssGSEA to compare immune infiltration between EMs patients and controls. Real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC) were performed to assess potential biomarker levels.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Thirty-three ERS-DEGs were identified, with nine HUB genes (<i>HSPA5, XBP1, HSP90B1, DNAJC3, PDIA3, PDIA6, PDIA4, HERPUD1</i>, and <i>MANF</i>) demonstrating diagnostic efficacy (AUC > 0.7). Furthermore, immune infiltration revealed a significant relationship between immune cell abundance and HUB gene expression. Experimental validation confirmed the consistency of four biomarkers (<i>HSPA5, HSP90B1, PDIA6</i>, and <i>HERPUD1</i>). Regulatory network analysis identified 62 miRNAs and 44 TFs interacting with HUB genes, suggesting a multifactorial immunometabolic axis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>We identified four biomarkers (<i>HSPA5, HSP90B1, PDIA6</i>, and <i>HERPUD1</i>) associated with ERS that offer new insights into the detection and treatment of EMs. Our findings indicate an abnormal response to ERS and immune system infiltration contribute to the progression of EMs.</p>\\n </section>\\n </div>\",\"PeriodicalId\":7665,\"journal\":{\"name\":\"American Journal of Reproductive Immunology\",\"volume\":\"93 5\",\"pages\":\"\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-05-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70092\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Reproductive Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/aji.70092\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Reproductive Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/aji.70092","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Deciphering the Molecular Crosstalk of Endoplasmic Reticulum Stress and Immune Infiltration in Endometriosis
Background
Endometriosis (EMs), characterized by ectopic endometrial growth causing infertility. Endoplasmic reticulum stress (ERS) is an important cellular defense mechanism. However, the correlation between ERS and EMs remains unclear. We aimed to investigate the relationship between them, identify biomarkers, and offer new insights into the treatment of EMs.
Methods
Two RNA expression datasets (GSE120103 and GSE25628) related to EMs in Homo sapiens were used to identify ERS-differentially expressed genes (ERS-DEGs). Protein–protein interaction (PPI) networks and CytoHubba (Cytoscape) identified ERS-associated HUB genes, with receiver operating characteristic curves (ROC) evaluating diagnostic value. Constructed mRNA-microRNA (miRNA)/RNA-transcription factor (TF) interaction networks and performed ssGSEA to compare immune infiltration between EMs patients and controls. Real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC) were performed to assess potential biomarker levels.
Results
Thirty-three ERS-DEGs were identified, with nine HUB genes (HSPA5, XBP1, HSP90B1, DNAJC3, PDIA3, PDIA6, PDIA4, HERPUD1, and MANF) demonstrating diagnostic efficacy (AUC > 0.7). Furthermore, immune infiltration revealed a significant relationship between immune cell abundance and HUB gene expression. Experimental validation confirmed the consistency of four biomarkers (HSPA5, HSP90B1, PDIA6, and HERPUD1). Regulatory network analysis identified 62 miRNAs and 44 TFs interacting with HUB genes, suggesting a multifactorial immunometabolic axis.
Conclusions
We identified four biomarkers (HSPA5, HSP90B1, PDIA6, and HERPUD1) associated with ERS that offer new insights into the detection and treatment of EMs. Our findings indicate an abnormal response to ERS and immune system infiltration contribute to the progression of EMs.
期刊介绍：
The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
