Metabolomic Urine Profile: Searching for New Biomarkers of SDHx-Associated Pheochromocytomas and Paragangliomas

• Type: Article in International Scientific Journal
• Date: 2019

Authors

R Martins (Author) FMUP; Goncalves, LG (Author) Other; Cunha, N (Author) Other; Bugalho, MJ (Author) Other

Journal

Title: Journal of Clinical Endocrinology and Metabolism

Vol. 104

Pages: 5467-5477

ISSN: 0021-972X

Publisher: Endocrine Society

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00R-537

DOI: 10.1210/jc.2019-01101

Abstract (EN): Context: Metabolomic studies of pheochromocytoma and paraganglioma tissue showed a correlation between metabolomic profile and presence of SDHx mutations, especially a pronounced increase of succinate. Objective: To compare the metabolomic profile of 24-hour urine samples of SDHx mutation carriers with tumors (affected mutation carriers), without tumors (asymptomatic mutation carriers), and patients with sporadic pheochromocytomas and paragangliomas. Methods: Proton nuclear magnetic resonance spectroscopic profiling of urine samples and metabolomic analysis using pairwise comparisons were complemented by metabolite set enrichment analysis to identify meaningful patterns. Results: The urine of the affected SDHx carriers showed substantially lower levels of seven metabolites than the urine of asymptomatic mutation carriers (including, succinate and N-acetylaspartate). The urine of patients with SDHx-associated tumors presented substantially higher levels of three metabolites compared with the urine of patients without mutation; the metabolite set enrichment analysis identified gluconeogenesis, pyruvate, and aspartate metabolism as the pathways that most probably explained the differences found. N-acetylaspartate was the only metabolite the urinary levels of which were significantly different between the three groups. Conclusions: The metabolomic urine profile of the SDHx mutation carriers with tumors is different from that of asymptomatic carriers and from that of patients with sporadic neoplasms. Differences are likely to reflect the altered mitochondria energy production and pseudohypoxia signature of these tumors. The urinary levels of N-acetylaspartate and succinate contrast with those reported in tumor tissue, suggesting a defective washout process of oncometabolites in association with tumorigenesis. The role of N-acetylaspartate as a tumor marker for these tumors merits further investigation.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11