Identification of Novel Serum Metabolic Biomarkers as Indicators in the Progression of Intravenous Leiomyomatosis: A High Performance Liquid Chromatography-Tandem Mass Spectrometry-Based Study

BACKGROUND: Intravenous leiomyomatosis (IVL) is a rare estrogen-dependent neoplasm. However, identifiable and reliable biomarkers are still not available for clinical application, especially for the diagnosis and prognosis of the disease. METHODS: In the present study, 30 patients with IVL and 30 healthy controls were recruited. Serum samples were isolated from these participants for further high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis to study metabolomics alterations and identify differentially expressed metabolites based on orthogonal partial least-squares discriminant analysis (OPLS-DA). Subsequently, lasso regression analysis and a generalized linear regression model were applied to screen out hub metabolites associated with the progression of IVL. RESULTS: First, 16 metabolites in the positive ion mode were determined from the 240 identifiable metabolites at the superclass level, with ten metabolites upregulated in the IVL group and the remaining six metabolites downregulated. Our data further proved that four metabolites [hypoxanthine, acetylcarnitine, glycerophosphocholine, and hydrocortisone (cortisol)] were closely related to the oncogenesis of IVL. Hypoxanthine and glycerophosphocholine might function as protective factors in the development of IVL (OR = 0.19 or 0.02, respectively). Nevertheless, acetylcarnitine and hydrocortisone (cortisol), especially the former, might serve as risk indicators for the disease to promote the development or recurrence of IVL (OR = 18.16 or 2.10, respectively). The predictive accuracy of these hub metabolites was further validated by the multi-class receiver operator characteristic curve analysis (ROC) with the Scikit-learn algorithms. CONCLUSION: Four hub metabolites were finally determined via comprehensive bioinformatics analysis, and these substances could potentially serve as novel biomarkers in predicting the prognosis or progression of IVL.