Urine metabolomics for assessing fertility-sparing treatment efficacy in endometrial cancer: a non-invasive approach using ultra-performance liquid chromatography mass spectrometry.

OBJECTIVE

This study aimed to reveal the urine metabolic change of endometrial cancer (EC) patients during fertility-sparing treatment and establish non-invasive predictive models to identify patients with complete remission (CR).

METHOD

This study enrolled 20 EC patients prior to treatment (PT) and 22 patients with CR, aged 25-40 years. Eligibility criteria consisted of stage IA high-grade EC, lesions confined to endometrium, normal hepatic and renal function, normal urine test, no contraindication for fertility-sparing treatment and no prior therapy. Urine samples were analyzed using ultraperformance liquid chromatography mass spectrometry (UPLC-MS), a technique chosen for its high sensitivity and resolution, allows for rapid, accurate identification and quantification of metabolites, providing a comprehensive metabolic profile and facilitating the discovery of potential biomarkers. Analytical techniques were employed to determine distinct metabolites and altered metabolic pathways. The statistical analyses were performed using univariate and multivariate analyses, logistic regression and receiver operating characteristic (ROC) curves to discover and validate the potential biomarker models.

RESULTS

A total of 108 different urine metabolomes were identified between CR and PT groups. These metabolites were enriched in ascorbate and aldarate metabolism, one carbon pool by folate, and some amino acid metabolisms pathways. A panel consisting of Baicalin, 5beta-1,3,7 (11)-Eudesmatrien-8-one, Indolylacryloylglycine, Edulitine, and Physapubenolide were selected as biomarkers, which demonstrated the best predictive ability with the AUC values of 0.982/0.851 in training/10-fold-cross-validation group, achieving a sensitivity of 0.975 and specificity of 0.967, respectively.

CONCLUSION

The urine metabolic analysis revealed the metabolic changes in EC patients during the fertility-sparing treatment. The predictive biomarkers present great potential diagnostic value in fertility-sparing treatments for EC patients, offering a less invasive means of monitoring treatment efficacy. Further research should explore the mechanistic underpinnings of these metabolic changes and validate the biomarker panel in larger, diverse populations due to the small sample size and single-institution nature of our study.