Journal Article

Global metabolomic profiling of uterine leiomyomas

Pitkänen, Esa, Heinonen, Hanna-Riikka, Bützow, Ralf, Kaasinen, Eevi, Pasanen, Annukka, Sjöberg, Jari, Karhu, Auli, Sarvilinna, Nanna S, Heikinheimo, Oskari, Aaltonen, Lauri A, Mäkinen, Netta, Mehine, Miika

2017

Overview

Background: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH . The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas. Methods: We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography–tandem mass spectroscopy. Results: A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the FH subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the FH subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for FH deficiency. In contrast, leiomyomas of the MED12 subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data. Conclusions: The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/208/199 / 631/67/1857 / 631/80/304 / 692/4017 / 692/699/2768 / Adenosine - analogs & derivatives / Adenosine - metabolism / Amino acids / Amino Acids - metabolism / Argininosuccinic Acid - metabolism / Ascorbic acid / Ascorbic Acid - metabolism / Biomedical and Life Sciences / Biomedicine / Cancer Research / Citric Acid Cycle / Drug Resistance / Epidemiology / Female / Fibroids / Fumarate Hydratase - genetics / Gene expression / Genetics & Genomics / genetics-and-genomics / HMGA2 Protein - genetics / Humans / Leiomyoma - genetics / Leiomyoma - metabolism / Lipid Metabolism / Liquid chromatography / Mass spectroscopy / Mediator Complex - genetics / Metabolic Networks and Pathways / Metabolic pathways / Metabolism / Metabolites / Metabolome / Metabolomics / Molecular Medicine / Myometrium / Oncology / Pentose Phosphate Pathway / Succinyladenosine / Tricarboxylic acid cycle / Tumors / Uterine Neoplasms - genetics / Uterine Neoplasms - metabolism / Uterus / Vitamin A / Vitamin A - metabolism