Integrated Analysis of Lactate-Related Genes Identifies S100A4 as a Novel Marker Promoting the Migration and Invasion of Endometrial Stromal Cell in Endometriosis

Endometriosis is a prevalent gynecological disorder worldwide that significantly impairs the quality of life of patients and imposes a substantial economic burden. The limited efficacy and adverse effects of current pharmacological and surgical treatments highlight the urgent need for alternative diagnostic biomarkers and therapeutic targets. Recent evidence indicates that metabolic reprogramming, particularly lactate metabolism, plays a crucial role in the development and progression of endometriosis. In this study, we employed differential expression analysis to identify differentially expressed genes in endometriosis patients, and used Least Absolute Shrinkage and Selection Operator (LASSO) regression and Random Forest (RF) for feature selection and model construction. Five key genes (MRPS2, YARS2, SLC3A1, CALD1, and S100A4) were validated as highly accurate diagnostic markers. Furthermore, we conducted in-depth analysis of the regulatory activity of these key lactate metabolism-related genes and their association with immune infiltration. Additionally, we constructed a lncRNA-miRNA gene regulatory network, providing insights into the molecular mechanisms and potential therapeutic strategies. Among these key lactate metabolism-related genes, S100A4 was found to be significantly upregulated in the lesions of endometriosis and plays a pivotal role in regulating cellular invasion and metabolic reprogramming in endometriosis. Silencing of S100A4 significantly inhibited the migration and invasion ability of endometrial stromal cells, whereas overexpression of S100A4 reversed this inhibitory effect. This finding further underscores the importance of S100A4 as a potential therapeutic target. In conclusion, this study highlights the potential value of lactate-related genes as diagnostic biomarkers and therapeutic targets, especially targeting the S100A4 gene in endometrial stromal cells, which may serve as an effective therapeutic strategy to inhibit the progression of endometriosis, offering new directions for future clinical diagnosis and treatment. Similar content being viewed by others Data Availability All data are available in the article or its supporting information, further inquiries can be directed to the corresponding authors.

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We would like to thank all patients who agreed to participate in this study and all colleagues who helped with this research. Funding This work was supported by grants from the National Natural Science Foundation of China (no. 82001524 and no. 8257063225 to Hengwei Liu), the Natural Science Foundation of Hubei Province (no. 2020CFB310 to Hengwei Liu), the Traditional Chinese Medicine Hospital of Wuxue City scientific research project (no. 2023A005 to Yanyun Wu). Author information Authors and Affiliations Contributions X.P.W and Y.C. contributed equally to this work. X.P.W and Y.C. completed the molecular biology experiments and data collection, analysis and was the major contributor in writing the manuscript. X.P.W., Q.Y.W. and X.W.W. contributed to clinical sample collection. X.P.W, Y.C, Q.Y.W, H.W.L and Y.Y.W reviewed and polished the manuscript. H.W.L and Y.Y.W designed the study and to data acquisition. All authors reviewed and approved the final manuscript. Corresponding authors Ethics declarations Ethics Approval and Consent to Participate Approval by Ethics Committee: The Research Ethics Committee of Tongji Medical College, Huazhong University of Science (IORG 140 No: IORG0003571). Human rights statements and informed consent: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and its later amendments. Informed consent was obtained from all patients for inclusion in the study. Competing Interests The authors declare that they have 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 Wang, X., Chen, Y., Wu, Q. et al. Integrated Analysis of Lactate-Related Genes Identifies S100A4 as a Novel Marker Promoting the Migration and Invasion of Endometrial Stromal Cell in Endometriosis. Reprod. Sci. 32, 2558–2573 (2025). https://doi.org/10.1007/s43032-025-01914-7 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-025-01914-7