Extracellular Trap-Related Genes as Potential Diagnostic Biomarkers for Endometriosis

Fang YX, He YF, Wang BB, He J, Dong Y, Chen G, Zhou SG
In: International Journal of Women's Health, Vol Volume 17, Iss Issue 1, Pp 4497-4517 (2025) · 2025 · W7106208045
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Using machine learning on the GSE141549 dataset, researchers identified CEACAM1, FOS, PLA2G2A, and THBS1 as robust diagnostic biomarkers for endometriosis with high predictive accuracy.

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This study leverages machine learning algorithms to identify neutrophil extracellular trap-related genes as potential diagnostic biomarkers for endometriosis. By analyzing the GSE141549 dataset, the researchers pinpointed four key genes—CEACAM1, FOS, PLA2G2A, and THBS1—and constructed a diagnostic model that demonstrated high accuracy and robust generalizability across multiple external cohorts. The findings suggest that these biomarkers are associated with immune infiltration and could facilitate the development of non-invasive early detection strategies for the disease. This paper is centrally about endometriosis — specifically focusing on identifying novel genetic biomarkers for its diagnosis.

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Abstract

Ya-Xing Fang,1– 3,* Yu-Feng He,1– 3,* Bing-Bing Wang,1– 3,* Juan He,1,2 Yang Dong,1,2 Guo Chen,1– 3 Shu-Guang Zhou3– 6 1Department of Obstetrics and Gynecology, Maternity and Child Healthcare Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230001, People’s Republic of China; 2Department of Gynecology, Anhui Women and Children’s Medical Center, Hefei, Anhui, 230001, People’s Republic of China; 3Department of Obstetrics and Gynecology, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 4Department of Obstetrics and Gynecology, Anhui Maternal and Child Health Hospital, Hefei, Anhui, 230051, People’s Republic of China; 5Department of Obstetrics and Gynecology, Anhui Provincial Children’s Hospital, Hefei, Anhui, 230051, People’s Republic of China; 6School of Public Health, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu-Guang Zhou, Email [email protected] Guo Chen, Email [email protected]: Endometriosis (EM), a prevalent gynecological disorder in reproductive-age women, lacks reliable noninvasive diagnostic tools. EM may be detected by neutrophil extracellular traps (NETs), which are essential to inflammation and immunological regulation. This research utilized 13 machine learning algorithms to improve the predictive precision of the diagnostic model and pinpointed four potential biomarkers that could aid in the diagnosis of EM.Methods: Using the GSE141549 dataset, we combined differentially expressed genes with NETs-related markers to identify key genes linked to EM. We performed functional analysis to understand their biological roles. Through 13 machine learning methods, we built 107 different models and selected four central genes: CEACAM1, FOS, PLA2G2A, and THBS1. We developed a diagnostic model, evaluating its performance with ROC curves, calibration plots, and decision curve analysis; its robustness was rigorously assessed through 10-fold cross-validation.Results: The four-gene model demonstrated superior performance, with high accuracy in the training set (AUC: 0.962), robust generalizability in cross-validation (mean AUC: 0.975) and external cohorts, confirmed clinical utility, and consistent gene expression across multiple datasets.Conclusion: This study identifies CEACAM1, FOS, PLA2G2A, and THBS1 as promising biomarkers for endometriosis. Their association with immune infiltration may improve early detection strategies, highlighting the potential for developing non-invasive diagnostic tools for EM in the future.Keywords: endometriosis, neutrophil extracellular traps, machine learning, prediction, diagnosis
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International Journal of Women's Health (Nov 2025) Extracellular Trap-Related Genes as Potential Diagnostic Biomarkers for Endometriosis Abstract Ya-Xing Fang,1– 3,* Yu-Feng He,1– 3,* Bing-Bing Wang,1– 3,* Juan He,1,2 Yang Dong,1,2 Guo Chen,1– 3 Shu-Guang Zhou3– 6 1Department of Obstetrics and Gynecology, Maternity and Child Healthcare Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230001, People’s Republic of China; 2Department of Gynecology, Anhui Women and Children’s Medical Center, Hefei, Anhui, 230001, People’s Republic of China; 3Department of Obstetrics and Gynecology, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 4Department of Obstetrics and Gynecology, Anhui Maternal and Child Health Hospital, Hefei, Anhui, 230051, People’s Republic of China; 5Department of Obstetrics and Gynecology, Anhui Provincial Children’s Hospital, Hefei, Anhui, 230051, People’s Republic of China; 6School of Public Health, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu-Guang Zhou, Email [email protected] Guo Chen, Email [email protected]: Endometriosis (EM), a prevalent gynecological disorder in reproductive-age women, lacks reliable noninvasive diagnostic tools. EM may be detected by neutrophil extracellular traps (NETs), which are essential to inflammation and immunological regulation. This research utilized 13 machine learning algorithms to improve the predictive precision of the diagnostic model and pinpointed four potential biomarkers that could aid in the diagnosis of EM.Methods: Using the GSE141549 dataset, we combined differentially expressed genes with NETs-related markers to identify key genes linked to EM. We performed functional analysis to understand their biological roles. Through 13 machine learning methods, we built 107 different models and selected four central genes: CEACAM1, FOS, PLA2G2A, and THBS1. We developed a diagnostic model, evaluating its performance with ROC curves, calibration plots, and decision curve analysis; its robustness was rigorously assessed through 10-fold cross-validation.Results: The four-gene model demonstrated superior performance, with high accuracy in the training set (AUC: 0.962), robust generalizability in cross-validation (mean AUC: 0.975) and external cohorts, confirmed clinical utility, and consistent gene expression across multiple datasets.Conclusion: This study identifies CEACAM1, FOS, PLA2G2A, and THBS1 as promising biomarkers for endometriosis. Their association with immune infiltration may improve early detection strategies, highlighting the potential for developing non-invasive diagnostic tools for EM in the future.Keywords: endometriosis, neutrophil extracellular traps, machine learning, prediction, diagnosis

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