J Clin Endocrinol Metab. 2021 Dec 14:dgab885. doi: 10.1210/clinem/dgab885. Online ahead of print.
ABSTRACT
CONTEXT: 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.
OBJECTIVES: We aimed to systematically characterize the metabolome alteration associated with TIO.
METHODS: 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). In order to screen and evaluate potential biomarkers, statistical analyses, pathway enrichment and receiver operating characteristic (ROC) were performed.
RESULTS: 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.
CONCLUSIONS: Metabolite profiling of TIO altered significant compared with HC. A high sensitivity and specificity panel with 5 oxylipins were tested as diagnostic predictor. 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.
PMID:34904633 | DOI:10.1210/clinem/dgab885
