Global metabolomic profiling of uterine leiomyomas.

Abstract

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.

• Authors: Hanna-Riikka Heinonen, Miika Mehine, Netta Mäkinen, Annukka Pasanen, Esa Pitkänen, Auli Karhu, Nanna S Sarvilinna, Jari Sjöberg, Oskari Heikinheimo, Ralf Bützow, Lauri A Aaltonen, Eevi Kaasinen
• Journal: British journal of cancer (Br J Cancer) Vol. 117 Issue 12 Pg. 1855-1864 (Dec 05 2017) ISSN: 1532-1827 [Electronic] England
• PMID: 29073636 (Publication Type: Journal Article)

Chemical References

• Amino Acids
• HMGA2 Protein
• MED12 protein, human
• Mediator Complex
• Vitamin A
• Argininosuccinic Acid
• succinyladenosine
• Fumarate Hydratase
• Adenosine
• Ascorbic Acid

Topics

• Adenosine (analogs & derivatives, metabolism)
• Amino Acids (metabolism)
• Argininosuccinic Acid (metabolism)
• Ascorbic Acid (metabolism)
• Citric Acid Cycle
• Female
• Fumarate Hydratase (genetics)
• HMGA2 Protein (genetics)
• Humans
• Leiomyoma (genetics, metabolism)
• Lipid Metabolism
• Mediator Complex (genetics)
• Metabolic Networks and Pathways
• Metabolome
• Pentose Phosphate Pathway
• Uterine Neoplasms (genetics, metabolism)
• Vitamin A (metabolism)