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Tissue-Based Metabolomics to Analyze the Breast Cancer Metabolome

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Metabolism in Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 207))

Abstract

Mass spectrometry and nuclear magnetic resonance-based metabolomics have been developed into mature technologies that can be utilized to analyze hundreds of biological samples in a high-throughput manner. Over the past few years, both technologies were utilized to analyze large cohorts of fresh frozen breast cancer tissues. Metabolite biomarkers were shown to separate breast cancer tissues from normal breast tissues with high sensitivity and specificity. Furthermore, the metabolome differed between hormone receptor positive (HR+) and hormone receptor negative (HR−) breast cancer, but was unchanged in HER2+ tumors compared to HER2− tumors. New metabolism-related biomarkers were discovered including the 4-aminobutyrate aminotransferase ABAT, where low mRNA expression led to an accumulation of beta-alanine and shortened relapse-free survival. The glutamate-to-glutamine ratio (GGR) represents another new biomarker that was increased in 88 % of HR− tumors and 56 % of HR+ tumors compared to normal breast tissues. The GGR might help to stratify patients for the treatment with specific glutaminase inhibitors that were recently developed and are currently being tested in phase I clinical studies. Surprisingly, 2-hydroxyglutarate (2-HG), initially found to accumulate in isocitrate dehydrogenase (IDH) mutated gliomas and leukemias and described as an oncometabolite, was detected to be drastically increased in several breast carcinomas in the absence of IDH mutations. In summary, metabolomics analysis of breast cancer tissues is a reliable method and has produced many new biological insights that may impact breast cancer diagnostics and treatment over the coming years.

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Abbreviations

2-HG:

2-hydroxyglutarate

ABAT:

4-aminobutyrate aminotransferase

CMP:

Cytidine-monophosphate

Cer:

Ceramide

ER:

Estrogen receptor

FDG-PET:

Fluorodeoxyglucose positron emission tomography

FFPE:

Formalin fixation and subsequent paraffin embedding

GC-TOF-MS:

Gas chromatography combined with time-of-flight mass spectrometry: a metabolomics platform suitable to investigate up to 200 identified metabolites of the primary metabolism

GGR:

Glutamate-to-glutamine ratio

GLS:

Glutaminase 1

HR:

Hormone receptor

HR-MAS-NMR:

High-resolution magic-angle spinning nuclear magnetic resonance: a metabolomics platform for nondestructive tissue analysis

IDH1, IDH2:

Isocitrate dehydrogenase 1, isocitrate dehydrogenase 2

KEGG:

Kyoto encyclopedia genes and genomes

MS:

Mass spectrometry

NMR:

Nuclear magnetic resonance

PROFILE:

Projection from interaction lattice: a clustering method for the analysis of metabolite changes in the context of the network of enzymatic reactions

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PI:

Phosphatidylinositol

PgR:

Progesterone receptor

SM:

Sphingomyelin

TG:

Triglyceride

UP-LC-MS:

Ultra performance liquid chromatography combined with mass spectrometry: a metabolomics platform for the analysis of up to 300 identified complex lipids

XDH:

Xanthine dehydrogenase

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Authors and Affiliations

  1. Institute of Pathology, Charité—Universitätsmedizin Berlin, Berlin, Germany

    Jan Budczies & Carsten Denkert

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  1. Jan Budczies
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  2. Carsten Denkert
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Correspondence to Jan Budczies .

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Editors and Affiliations

  1. RWTH University Hospital, Molecular Tumor Biology, Pauwelsstrasse 30, 52074 , Aachen, Germany

    Thorsten Cramer

  2. Dept. of Hematology and Oncology, Charité, Berlin, Germany

    Clemens A. Schmitt

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Budczies, J., Denkert, C. (2016). Tissue-Based Metabolomics to Analyze the Breast Cancer Metabolome. In: Cramer, T., A. Schmitt, C. (eds) Metabolism in Cancer. Recent Results in Cancer Research, vol 207. Springer, Cham. https://doi.org/10.1007/978-3-319-42118-6_7

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  • DOI: https://doi.org/10.1007/978-3-319-42118-6_7

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