Reduced type 2 epithelial-mesenchymal transition serves as a risk factor for the progression from endometriosis to endometriosis-associated ovarian cancer

Endometriosis-associated ovarian cancer (EAOC) is a rare subtype of ovarian cancer arising from the malignant transformation of endometriosis (EMS). Despite growing clinical awareness, its underlying pathogenic mechanisms are not fully understood. Epithelial-mesenchymal transition (EMT) plays a crucial role in the progression of various diseases, but the specific EMT changes in EAOC formation remain unclear. We retrieved transcriptomic data for EAOC and single-cell data for EMS from public databases and systematically analyzed EMT levels, EMT subtypes, and factors inducing EMT in both EMS and EAOC. Immunohistochemistry and Masson staining further validated the EMT and fibrosis levels in both EMS and EAOC. The study found that the overall EMT levels in EAOC were significantly lower than in EMS, primarily due to the reduction in type 2 EMT levels associated with fibrosis. Furthermore, this study indicated that the abundant C7 fibroblasts in EMS lesions might contribute to epithelial cell proliferation and EMT. However, the abundance of C7 fibroblasts was significantly reduced in EAOC, suggesting its potential regulatory role in EMT. We found that, during the progression from EMS to EAOC, the level of type 2 EMT decreased, and we also discovered that C7 fibroblasts could act as potential regulators of EMT. These findings expand our understanding of the malignant transformation of EAOC and provide new insights for the development of new diagnostic and therapeutic strategies. Similar content being viewed by others Abbreviations - EAOC: - Endometriosis-associated ovarian cancer - EMS: - Endometriosis - EMT: - Epithelial–mesenchymal transition - ECM: - Extracellular matrix - AtyEm: - Atypical endometriosis - AdjEm: - Endometriosis adjacent to endometriosis-associated ovarian cancer - Eutopic: - Endometriosis endometrium - Ectopic Ovary: - Ovarian endometriosis - Ectopic Peritoneal: - Peritoneal endometriosis - Ectopic Peritoneal Adjacent: - Peritoneal tissue adjacent to endometriosis

We gratefully acknowledge the financial support provided by the Third Affiliated Hospital of Guangzhou Medical University for this study. We also extend our sincere appreciation to all participants for their generous contribution of time and effort, which was instrumental in the successful completion of this research. Funding This study was funded by the General Program Fund of the Science and Technology Innovation Commission of Guangzhou (grant number 206206). Author information Authors and Affiliations Corresponding author Ethics declarations Ethical approval This study was approved by the Ethics Committee of the Third Affiliated Hospital of Guangzhou Medical University (Approval Number: MedEthics Committee Review [2021] No. 34). All the tissue samples used in this study were obtained from the biological sample bank of the Third Affiliated Hospital of Guangzhou Medical University. All patients who provided samples for the immunohistochemical experiments and Masson staining experiments signed written informed consent forms. Moreover, this study was conducted strictly in accordance with the ethical principles stipulated in the Helsinki Declaration (1975 edition) and its subsequent revisions. 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 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Liu, Y., Yin, D., Wu, L. et al. Reduced type 2 epithelial-mesenchymal transition serves as a risk factor for the progression from endometriosis to endometriosis-associated ovarian cancer. Sci Rep (2026). https://doi.org/10.1038/s41598-026-51155-0 Received: Accepted: Published: DOI: https://doi.org/10.1038/s41598-026-51155-0