{"title":"揭示子宫内膜异位症的潜在生物标志物：转录组学和单细胞分析。","authors":"Yuqiu Liu, Guanwen Gao, Wei Tian, Qingfeng Lv, Degao Liu, Changzhong Li","doi":"10.3389/fmed.2025.1528434","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The link between programmed cell death (PCD) and mitochondria has been documented in various diseases. However, its role in endometriosis (EMS) remains unexplored. This study aims to identify potential biomarkers in EMS associated with both PCD and mitochondrial functions.</p><p><strong>Methods: </strong>This analysis incorporates datasets related to EMS, PCD-related genes (PCD-RGs), and mitochondria-related genes (MRGs) sourced from public repositories. To uncover potential biomarkers, differential expression analysis, weighted gene co-expression network analysis (WGCNA), Boruta feature selection, expression validation, and diagnostic assessments were conducted. Functional analyses, immune infiltration profiling, and the construction of regulatory networks further elucidated the mechanisms through which these biomarkers may influence EMS. Finally, single-cell data were leveraged to examine the expression and functionality of these biomarkers at a granular level.</p><p><strong>Results: </strong>Apoptosis-inducing factor mitochondria-associated 1 (AIFM1) and pyruvate dehydrogenase kinase 4 (PDK4) were identified as potential biomarkers, with PDK4 upregulated and AIFM1 downregulated in EMS. Both genes demonstrated strong diagnostic potential. Enrichment analyses indicated their involvement in pathways associated with the cell cycle. Immune infiltration analyses revealed that AIFM1 had a significant positive correlation with resting dendritic cells and a negative correlation with M2 macrophages, whereas PDK4 was positively associated with M2 macrophages and inversely related to follicular helper T cells. Moreover, AIFM1 and PDK4 were regulated by 16 miRNAs (e.g., hsa-mir-16-5p) and 18 lncRNAs (e.g., LINC00294). Single-cell analysis further revealed dynamic expression trends of these potential biomarkers across cell differentiation stages, including gametocytes, monocytes, mesenchymal stem cells, and neutrophils.</p><p><strong>Conclusion: </strong>In this study, potential biomarkers (AIFM1 and PDK4) related to PCD and mitochondria were identified in EMS, offering valuable insights for the diagnosis and therapeutic strategies for the disease.</p>","PeriodicalId":12488,"journal":{"name":"Frontiers in Medicine","volume":"12 ","pages":"1528434"},"PeriodicalIF":3.1000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078282/pdf/","citationCount":"0","resultStr":"{\"title\":\"Uncovering potential biomarkers of endometriosis: transcriptomic and single-cell analysis.\",\"authors\":\"Yuqiu Liu, Guanwen Gao, Wei Tian, Qingfeng Lv, Degao Liu, Changzhong Li\",\"doi\":\"10.3389/fmed.2025.1528434\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The link between programmed cell death (PCD) and mitochondria has been documented in various diseases. However, its role in endometriosis (EMS) remains unexplored. This study aims to identify potential biomarkers in EMS associated with both PCD and mitochondrial functions.</p><p><strong>Methods: </strong>This analysis incorporates datasets related to EMS, PCD-related genes (PCD-RGs), and mitochondria-related genes (MRGs) sourced from public repositories. To uncover potential biomarkers, differential expression analysis, weighted gene co-expression network analysis (WGCNA), Boruta feature selection, expression validation, and diagnostic assessments were conducted. Functional analyses, immune infiltration profiling, and the construction of regulatory networks further elucidated the mechanisms through which these biomarkers may influence EMS. Finally, single-cell data were leveraged to examine the expression and functionality of these biomarkers at a granular level.</p><p><strong>Results: </strong>Apoptosis-inducing factor mitochondria-associated 1 (AIFM1) and pyruvate dehydrogenase kinase 4 (PDK4) were identified as potential biomarkers, with PDK4 upregulated and AIFM1 downregulated in EMS. Both genes demonstrated strong diagnostic potential. Enrichment analyses indicated their involvement in pathways associated with the cell cycle. Immune infiltration analyses revealed that AIFM1 had a significant positive correlation with resting dendritic cells and a negative correlation with M2 macrophages, whereas PDK4 was positively associated with M2 macrophages and inversely related to follicular helper T cells. Moreover, AIFM1 and PDK4 were regulated by 16 miRNAs (e.g., hsa-mir-16-5p) and 18 lncRNAs (e.g., LINC00294). Single-cell analysis further revealed dynamic expression trends of these potential biomarkers across cell differentiation stages, including gametocytes, monocytes, mesenchymal stem cells, and neutrophils.</p><p><strong>Conclusion: </strong>In this study, potential biomarkers (AIFM1 and PDK4) related to PCD and mitochondria were identified in EMS, offering valuable insights for the diagnosis and therapeutic strategies for the disease.</p>\",\"PeriodicalId\":12488,\"journal\":{\"name\":\"Frontiers in Medicine\",\"volume\":\"12 \",\"pages\":\"1528434\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078282/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fmed.2025.1528434\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fmed.2025.1528434","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Uncovering potential biomarkers of endometriosis: transcriptomic and single-cell analysis.
Background: The link between programmed cell death (PCD) and mitochondria has been documented in various diseases. However, its role in endometriosis (EMS) remains unexplored. This study aims to identify potential biomarkers in EMS associated with both PCD and mitochondrial functions.
Methods: This analysis incorporates datasets related to EMS, PCD-related genes (PCD-RGs), and mitochondria-related genes (MRGs) sourced from public repositories. To uncover potential biomarkers, differential expression analysis, weighted gene co-expression network analysis (WGCNA), Boruta feature selection, expression validation, and diagnostic assessments were conducted. Functional analyses, immune infiltration profiling, and the construction of regulatory networks further elucidated the mechanisms through which these biomarkers may influence EMS. Finally, single-cell data were leveraged to examine the expression and functionality of these biomarkers at a granular level.
Results: Apoptosis-inducing factor mitochondria-associated 1 (AIFM1) and pyruvate dehydrogenase kinase 4 (PDK4) were identified as potential biomarkers, with PDK4 upregulated and AIFM1 downregulated in EMS. Both genes demonstrated strong diagnostic potential. Enrichment analyses indicated their involvement in pathways associated with the cell cycle. Immune infiltration analyses revealed that AIFM1 had a significant positive correlation with resting dendritic cells and a negative correlation with M2 macrophages, whereas PDK4 was positively associated with M2 macrophages and inversely related to follicular helper T cells. Moreover, AIFM1 and PDK4 were regulated by 16 miRNAs (e.g., hsa-mir-16-5p) and 18 lncRNAs (e.g., LINC00294). Single-cell analysis further revealed dynamic expression trends of these potential biomarkers across cell differentiation stages, including gametocytes, monocytes, mesenchymal stem cells, and neutrophils.
Conclusion: In this study, potential biomarkers (AIFM1 and PDK4) related to PCD and mitochondria were identified in EMS, offering valuable insights for the diagnosis and therapeutic strategies for the disease.
期刊介绍：
Frontiers in Medicine publishes rigorously peer-reviewed research linking basic research to clinical practice and patient care, as well as translating scientific advances into new therapies and diagnostic tools. Led by an outstanding Editorial Board of international experts, this multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
In addition to papers that provide a link between basic research and clinical practice, a particular emphasis is given to studies that are directly relevant to patient care. In this spirit, the journal publishes the latest research results and medical knowledge that facilitate the translation of scientific advances into new therapies or diagnostic tools. The full listing of the Specialty Sections represented by Frontiers in Medicine is as listed below. As well as the established medical disciplines, Frontiers in Medicine is launching new sections that together will facilitate
- the use of patient-reported outcomes under real world conditions
- the exploitation of big data and the use of novel information and communication tools in the assessment of new medicines
- the scientific bases for guidelines and decisions from regulatory authorities
- access to medicinal products and medical devices worldwide
- addressing the grand health challenges around the world
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