Serum Metabolomics Reveals Dysregulation and Diagnostic Potential of Oxylipins in Tumor-induced Osteomalacia.

Abstract

CONTEXT:

Excessive production of fibroblast growth factor 23 (FGF23) by a tumor is considered 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.

OBJECTIVE:

We aimed to systematically characterize the metabolome alteration associated with TIO.

METHODS:

By means of liquid chromatography-tandem mass spectrometry-based metabolomics, we analyzed the metabolic profile from 96 serum samples (32 from TIO patients at initial diagnosis, pairwise samples after tumor resection, and 32 matched healthy control (HC) 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 cohorts. Differential metabolites were screened and conducted to functional clustering and annotation. A significantly enriched pathway was found involving 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 algorithm (AUC = 0.951; 95% CI, 0.827-1). Supported vector machine modeling and partial least squares modeling were conducted to validate the predictive capabilities of the diagnostic panel.

CONCLUSION:

Metabolite profiling of TIO showed significant alterations compared with HC. A high-sensitivity and high-specificity panel with 5 oxylipins was 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.

• Authors: Yiyi Gong, Xiaolin Ni, Chenxi Jin, Xiang Li, Yujie Wang, Ou Wang, Mei Li, Xiaoping Xing, Zhihong Wu, Yan Jiang, Weibo Xia
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 107 Issue 5 Pg. 1383-1391 (04 19 2022) ISSN: 1945-7197 [Electronic] United States
• PMID: 34904633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Biomarkers
• Oxylipins

Topics

• Biomarkers (metabolism)
• Humans
• Metabolome (physiology)
• Metabolomics
• Osteomalacia
• Oxylipins
• Paraneoplastic Syndromes