title: Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue - a GC-TOFMS based metabolomics study.
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.
authors: Institute of Pathology, Charité University Hospital, 10117 Berlin, Germany. jan.budczies@charite.de
authors: Jan
authors: J
authors: Budczies
authors: Carsten
authors: C
authors: Denkert
authors: Berit M
authors: BM
authors: Müller
authors: Scarlet F
authors: SF
authors: Brockmöller
authors: Frederick
authors: F
authors: Klauschen
authors: Balazs
authors: B
authors: Györffy
authors: Manfred
authors: M
authors: Dietel
authors: Christiane
authors: C
authors: Richter-Ehrenstein
authors: Ulrike
authors: U
authors: Marten
authors: Reza M
authors: RM
authors: Salek
authors: Julian L
authors: JL
authors: Griffin
authors: Mika
authors: M
authors: Hilvo
authors: Matej
authors: M
authors: Orešič
authors: Gert
authors: G
authors: Wohlgemuth
authors: Oliver
authors: O
authors: Fiehn
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001940:Breast / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016000:Cluster Analysis; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D020404:Glycerophospholipids / Q000378:metabolism; D006801:Humans; D055432:Metabolomics / Q000379:methods*; D009361:Neoplasm Invasiveness; D009711:Nucleotides / Q000378:metabolism; D025341:Principal Component Analysis
chemical_list: D000596:Amino Acids; D005230:Fatty Acids, Nonesterified; D020404:Glycerophospholipids; D009711:Nucleotides