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Open Access Research article

Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue – a GC-TOFMS based metabolomics study

Jan Budczies1*, Carsten Denkert1, Berit M Müller1, Scarlet F Brockmöller1, Frederick Klauschen1, Balazs Györffy12, Manfred Dietel1, Christiane Richter-Ehrenstein3, Ulrike Marten4, Reza M Salek5, Julian L Griffin5, Mika Hilvo6, Matej Orešič6, Gert Wohlgemuth7 and Oliver Fiehn7

Author Affiliations

1 Institute of Pathology, Charité University Hospital, 10117 Berlin, Germany

2 Research Laboratory of Pediatrics and Nephrology, Hungarian Academy of Sciences, Budapest, Hungary

3 Interdisciplinary Breast Center, Charité University Hospital, 10117 Berlin, Germany

4 Institute of Pathology, DRK Kliniken Berlin, 12559 Berlin, Germany

5 Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, United Kingdom

6 VTT Technical Research Centre of Finland, Espoo, Finland

7 Genome Center, University of California Davis, Davis, CA, USA

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BMC Genomics 2012, 13:334  doi:10.1186/1471-2164-13-334

Published: 23 July 2012

Abstract

Background

Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS) is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far.

Results

A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468 metabolite peaks could be detected; out of these 368 (79%) were significantly changed between cancer and normal tissues (p<0.05 in training and validation set). Furthermore, 13 tumor and 7 normal tissue markers were identified that separated cancer from normal tissues with a sensitivity and a specificity of >80%. Two-metabolite classifiers, constructed as ratios of the tumor and normal tissues markers, separated cancer from normal tissues with high sensitivity and specificity. Specifically, the cytidine-5-monophosphate / pentadecanoic acid metabolic ratio was the most significant discriminator between cancer and normal tissues and allowed detection of cancer with a sensitivity of 94.8% and a specificity of 93.9%.

Conclusions

For the first time, a comprehensive metabolic map of breast cancer was constructed by GC-TOF analysis of a large cohort of breast cancer and normal tissues. Furthermore, our results demonstrate that spectrometry-based approaches have the potential to contribute to the analysis of biopsies or clinical tissue samples complementary to histopathology.

Keywords:
Breast cancer; Metabolomics; Gas chromatography; Mass spectrometry; Cancer detection