{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T18:22:28Z","timestamp":1793989348088,"version":"4.8.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1528434","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T05:39:58Z","timestamp":1746077998000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Uncovering potential biomarkers of endometriosis: transcriptomic and single-cell 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