title: 1H-NMR based metabonomic profiling of human esophageal cancer tissue.
abstract: BACKGROUND
  The biomarker identification of human esophageal cancer is critical for its early diagnosis and therapeutic approaches that will significantly improve patient survival. Specially, those that involves in progression of disease would be helpful to mechanism research.
  
  
  METHODS
  In the present study, we investigated the distinguishing metabolites in human esophageal cancer tissues (n = 89) and normal esophageal mucosae (n = 26) using a (1)H nuclear magnetic resonance ((1)H-NMR) based assay, which is a highly sensitive and non-destructive method for biomarker identification in biological systems. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) were applied to analyse (1)H-NMR profiling data to identify potential biomarkers.
  
  
  RESULTS
  The constructed OPLS-DA model achieved an excellent separation of the esophageal cancer tissues and normal mucosae. Excellent separation was obtained between the different stages of esophageal cancer tissues (stage II = 28; stage III = 45 and stage IV = 16) and normal mucosae. A total of 45 metabolites were identified, and 12 of them were closely correlated with the stage of esophageal cancer. The downregulation of glucose, AMP and NAD, upregulation of formate indicated the large energy requirement due to accelerated cell proliferation in esophageal cancer. The increases in acetate, short-chain fatty acid and GABA in esophageal cancer tissue revealed the activation of fatty acids metabolism, which could satisfy the need for cellular membrane formation. Other modified metabolites were involved in choline metabolic pathway, including creatinine, creatine, DMG, DMA and TMA. These 12 metabolites, which are involved in energy, fatty acids and choline metabolism, may be associated with the progression of human esophageal cancer.
  
  
  CONCLUSIONS
  Our findings firstly identify the distinguishing metabolites in different stages of esophageal cancer tissues, indicating the attribution of metabolites disturbance to the progression of esophageal cancer. The potential biomarkers provide a promising molecular diagnostic approach for clinical diagnosis of human esophageal cancer and a new direction for the mechanism study.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Longqi
authors.initials: L
authors.lastname: Chen
authors.forename: Pengchi
authors.initials: P
authors.lastname: Deng
authors.forename: Qian
authors.initials: Q
authors.lastname: Bu
authors.forename: Pu
authors.initials: P
authors.lastname: Xiang
authors.forename: Manli
authors.initials: M
authors.lastname: Li
authors.forename: Wenjie
authors.initials: W
authors.lastname: Lu
authors.forename: Youzhi
authors.initials: Y
authors.lastname: Xu
authors.forename: Hongjun
authors.initials: H
authors.lastname: Lin
authors.forename: Tianming
authors.initials: T
authors.lastname: Wu
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Shao
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Cen
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000378:metabolism*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor
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