Serum Metabolites as Diagnostic Biomarkers in Patients with Endometriosis

Endometriosis diagnosis is usually delayed. The gold standard for diagnosing endometriosis is laparoscopy, which is invasive and accompanied by several risks. Currently, there are no effective non-invasive biomarkers for diagnosing endometriosis. Here, we investigated whether metabolites whose levels are altered in patients with endometriosis hold potential as diagnostic biomarkers for the disease. This case–control study involved 32 patients with endometriosis and 29 patients with other benign gynecological disease. The diagnosis of all patients was confirmed through postoperative histopathological examination, and the patients were divided into two groups: an endometriosis group (EM) and a control group. Fasting blood was collected and used for non-targeted metabolomic-based detection. The data were processed through principal component analysis, orthogonal partial least squares discriminant analysis, and significance analysis of microarrays. A univariate receiver operating characteristic curve was used to evaluate the diagnostic value of the metabolites. The metabolite profiles of patients with endometriosis were markedly different compared with those of the controls. In addition, several metabolic pathways, including biosynthesis of unsaturated fatty acids, arginine biosynthesis, and glutathione metabolism, were altered. Ornithine and medorinone showed better potential as biomarkers for endometriosis diagnosis than CA125. We analyzed the altered metabolic profiles in patients with endometriosis and found ornithine and medorinone as potential non-invasive biomarkers for endometriosis diagnosis, whereas the combined ornithine-medorinone diagnosis is more valuable. These findings may help advance research on non-invasive diagnostic biomarkers for endometriosis. Further research with an improved study design and a larger cohort should be performed to confirm the diagnostic potential and clinical application of these biomarkers. Similar content being viewed by others Data availability The data generated in this study will be shared on reasonable request to the corresponding author.

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We acknowledge Aksomics (Shanghai, China) for the support in LC-MS/MS and data analysis, and thank Ran Chu for assistance with data collection. Funding This study was funded by the National Key R&D Program of China (grant number 2022YFC2704000), the National Natural Science Foundation of China (grant number 82301855), the Major Basic Research of Natural Science Foundation of Shandong (grant number ZR2021ZD34), National Natural Science Foundation of China (grant number 82071621), and Natural Science Foundation of Shandong Province (grant number ZR2023QH186). The funders had not role in the design of the study; collection, analysis, and interpretation of data; writing of the report; and decision to submit the article for publication. Author information Authors and Affiliations Contributions Qiuju Li: conception and design of the study; collection of samples; acquisition, analysis and interpretation of data; drafting the article. Le Xu: collection of samples; acquisition, analysis and interpretation of data; revising the article. Ying Lin: collection of samples, analysis and interpretation of data, revising the article. Ming Yuan: conception and design of the study, collection of samples, revising the article. Xue Jiao: collection of the samples, acquisition of data, revising the article. Qianhui Ren: collection of samples, acquisition of data, revising the article. Dong Li: conception and design of the study, analysis and interpretation of data, revising the article. Guoyun Wang: conception and design of the study, revising the article. All authors: final approval of the version to be published and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Corresponding author Ethics declarations Conflicts of interest The authors report no conflict of interest. Research involving human participants ethics approval This study was approved by the Ethics Committee of Medical Integration and Practice Center at the Cheeloo College of Medicine, Shandong University [SDULCLL2022-1–21]. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Informed consent Informed consent was obtained from the patients before surgery. Consent to publish Not applicable. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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 Li, Q., Xu, L., Lin, Y. et al. Serum Metabolites as Diagnostic Biomarkers in Patients with Endometriosis. Reprod. Sci. 31, 3719–3728 (2024). https://doi.org/10.1007/s43032-024-01536-5 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-024-01536-5