Uncovering potential biomarkers of endometriosis: transcriptomic and single-cell analysis.

IF 3.1 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Frontiers in Medicine Pub Date : 2025-05-01 eCollection Date: 2025-01-01 DOI:10.3389/fmed.2025.1528434

Yuqiu Liu, Guanwen Gao, Wei Tian, Qingfeng Lv, Degao Liu, Changzhong Li

{"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":"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.","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}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

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。

背景：程序性细胞死亡（PCD）与线粒体之间的联系已在各种疾病中得到证实。然而，其在子宫内膜异位症（EMS）中的作用仍未被探索。本研究旨在确定EMS中与PCD和线粒体功能相关的潜在生物标志物。方法：本分析纳入了来自公共存储库的EMS、pcd相关基因（PCD-RGs）和线粒体相关基因（MRGs）相关数据集。为了发现潜在的生物标志物，进行了差异表达分析、加权基因共表达网络分析（WGCNA）、Boruta特征选择、表达验证和诊断评估。功能分析、免疫浸润分析和调控网络的构建进一步阐明了这些生物标志物可能影响EMS的机制。最后，利用单细胞数据在颗粒水平上检查这些生物标志物的表达和功能。结果：凋亡诱导因子线粒体相关1 （AIFM1）和丙酮酸脱氢酶激酶4 （PDK4）被确定为潜在的生物标志物，在EMS中PDK4上调，AIFM1下调。这两个基因都显示出很强的诊断潜力。富集分析表明它们参与与细胞周期相关的途径。免疫浸润分析显示AIFM1与静息树突状细胞呈显著正相关，与M2巨噬细胞呈负相关，而PDK4与M2巨噬细胞呈正相关，与滤泡辅助T细胞呈负相关。此外，AIFM1和PDK4受16种mirna（如hsa-mir-16-5p）和18种lncrna（如LINC00294）的调控。单细胞分析进一步揭示了这些潜在生物标志物在细胞分化阶段的动态表达趋势，包括配子体细胞、单核细胞、间充质干细胞和中性粒细胞。结论：本研究在EMS中发现了与PCD和线粒体相关的潜在生物标志物（AIFM1和PDK4），为该病的诊断和治疗策略提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Frontiers in Medicine Medicine-General Medicine

CiteScore

5.10

自引率

5.10%

发文量

3710

审稿时长

12 weeks

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