ETS Homologous Factor (EHF) and Gamma Linolenic Acid (GLA): novel strategies for early diagnosis and treatment of endometriosis

Endometriosis (EMs) affects the physical and mental health of a wide range of women of childbearing age. Exploring specific diagnostic targets and screening potential therapeutic drugs will help early diagnosis and improve prognosis. The diagnostic and therapeutic potential of ETS homologous factor (EHF) and Gamma linolenic acid (GLA) remains to be explored. Based on RNA sequencing of GEO datasets and local clinical samples, LASSO and SVM-RFE machine learning algorithms were used to screen out the key gene (EHF). Explore the expression level of EHF and its effects on the malignant biological behavior and regulatory mechanism of endometriosis cells (12z). Based on the positive and negative correlation genes of EHF, cMap analysis and molecular docking were performed to screen out the potential therapeutic drug (GLA). Explore the therapeutic effects of GLA on endometriosis in vivo and in vitro. EHF was abnormally low in endometriosis tissues and cells. Overexpression of EHF could inhibit malignant phenotypes such as cell proliferation, migration, invasion, and angiogenesis, and inhibit the PI3K/AKT/mTOR axis, leading to cell cycle arrest and inhibiting epithelial-mesenchymal transition (EMT). GLA could play a potential therapeutic role in vivo and in vitro with low normal cell toxicity. EHF is a potential protective gene for endometriosis, and its overexpression could inhibit the malignant biological phenotype, cell cycle and EMT by inhibiting the PI3K/AKT/mTOR axis. GLA screened based on EHF could be used as a potential therapeutic drug to play a therapeutic role in vitro and in vivo. This study screened and validated specific diagnostic targets (EHF) and potential therapeutic drugs (GLA) for endometriosis based on clinical tissue sample tissue, cells, RNA sequencing, in vivo and in vitro experiments to assist in the early diagnosis and prognosis improvement of EMs. Similar content being viewed by others Data availability The data can be obtained through the email under reasonable request: [email protected]. Abbreviations - Ems: - Endometriosis - EHF: - ETS homologous factor - GLA: - Gamma linolenic acid - GEO: - Gene Expression Omnibus - RNA-seq: - RNA sequencing - LASSO: - Least Absolute Shrinkage and Selection Operator - SVM: - Support Vector Machines - GO: - Gene Ontology - KEGG: - Kyoto Encyclopedia of Genes and Genomes - GSEA: - Gene Set Enrichment Analysis - 12z: - Human immortalized endometriosis cells - hEEC: - Human immortalized endometrial cells - cMap: - Connectivity Map - EMT: - Epithelial-Mesenchymal Transition

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Thanks for the support of The Third Affiliated Hospital of Zhengzhou University. Funding This work is supported by PhD research startup foundation of the Third Affiliated Hospital of Zhengzhou University (BS20230104). Henan Province Science and Technology Research Project (No. LHGJ20230372 and No. LHGJ20230051). National Natural Science Foundation of China (No. 82403992). National Natural Science Foundation of Henan (No. 242300421492). Author information Authors and Affiliations Contributions Mengjun Zhang and Jialin Wang contributed equally to this work. Design of the study were performed by MZ, XZ and LZ. Implementation of the experiment were performed by MZ, HY and JW. Data analysis were performed by ZZ. The first draft of the manuscript was written and revised by MZ, XZ and LZ. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Corresponding authors Ethics declarations Ethical approval and consent to participate The Ethics Review Committee of the Third Affiliated Hospital of Zhengzhou University reviewed and approved this study (No.: 2023–098; Date: April 28, 2023). All patients read and signed the informed consent form. Clinical trial number Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Zhang, M., Wang, J., Yue, H. et al. ETS Homologous Factor (EHF) and Gamma Linolenic Acid (GLA): novel strategies for early diagnosis and treatment of endometriosis. Funct Integr Genomics 26, 14 (2026). https://doi.org/10.1007/s10142-025-01792-x Received: Revised: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s10142-025-01792-x