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

BMC Genomics

Research Article

Reza M Salek¹  Julian L Griffin¹  Gert Wohlgemuth²  Oliver Fiehn²  Jan Budczies³  Manfred Dietel³  Berit M Müller³  Scarlet F Brockmöller³  Frederick Klauschen³  Carsten Denkert³  Balazs Györffy⁴  Ulrike Marten⁵  Christiane Richter-Ehrenstein⁶  Matej Orešič⁷  Mika Hilvo⁷ 

[1] Department of Biochemistry, University of Cambridge, CB2 1GA, Cambridge, United Kingdom;Genome Center, University of California Davis, Davis, CA, USA;Institute of Pathology, Charité University Hospital, 10117, Berlin, Germany;Institute of Pathology, Charité University Hospital, 10117, Berlin, Germany;Research Laboratory of Pediatrics and Nephrology, Hungarian Academy of Sciences, Budapest, Hungary;Institute of Pathology, DRK Kliniken Berlin, 12559, Berlin, Germany;Interdisciplinary Breast Center, Charité University Hospital, 10117, Berlin, Germany;VTT Technical Research Centre of Finland, Espoo, Finland;

关键词: Breast cancer;    Metabolomics;    Gas chromatography;    Mass spectrometry;    Cancer detection;   

DOI  :  10.1186/1471-2164-13-334

 received in 2011-11-30, accepted in 2012-07-23,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundChanges 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.ResultsA 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%.ConclusionsFor 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.

【 授权许可】

CC BY   
© Budczies et al.; licensee BioMed Central Ltd. 2012