Supplementary Materials for Serum metabolomics reveals dysregulation and diagnostic potential of oxylipins in tumor-induced osteomalacia

Excessive production of fibroblast growth factor 23 (FGF23) by tumor was considered as the main pathogenesis in tumor-induced osteomalacia (TIO). Despite its importance to comprehensive understanding of pathogenesis and diagnosis, the regulation of systemic metabolism in TIO remains unclear. By means of liquid chromatography-tandem mass spectrometry (LC-MS) based metabolomics, we analyzed the metabolic profile from 96 serum samples (32 initial diagnosis TIO patients, pairwise samples after tumor resection and 32 matched healthy control subjects). Metabolomic profiling revealed distinct alterations between TIO and HC cohort. Differential metabolites were screened and conducted to functional clustering and annotation. Significantly enriched pathway was found involved in arachidonic acid metabolism. A combination of 5 oxylipins, 4-HDoHE, leukotriene B4, 5-HETE, 17-HETE and 9,10,13-TriHOME, demonstrated a high sensitivity and specificity panel for TIO prediction screened by random forest (RF) algorithm (AUC=0.951, 95% confidence interval, CI 0.827-1). Supported vector machine (SVM) model and partial least-squares (PLS) model were conducted to validate the predictive capabilities of the diagnostic panel. In summary, for the first time, we provide the global profile of metabolomes and identify potential diagnostic biomarkers of TIO. The present work may offer novel insights into the pathogenesis of TIO.