title: ¹H NMR-based metabolic profiling of human rectal cancer tissue.
abstract: BACKGROUND
  Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis.
  
  
  METHODS
  Here, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer.
  
  
  RESULTS
  Excellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer.
  
  
  CONCLUSIONS
  Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would provide a promising molecular diagnostic approach for clinical diagnosis of human rectal cancer. The role and underlying mechanism of metabolites in rectal cancer progression are worth being further investigated.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Hailong
authors.initials: H
authors.lastname: Zhang
authors.forename: Pengchi
authors.initials: P
authors.lastname: Deng
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Zou
authors.forename: Wenjie
authors.initials: W
authors.lastname: Lu
authors.forename: Pu
authors.initials: P
authors.lastname: Xiang
authors.forename: Tianming
authors.initials: T
authors.lastname: Wu
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Shao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 17#, 3rd Section, Ren min South Road, Chengdu 610041, China. 381926959@qq.com.
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D008875:Middle Aged; D009367:Neoplasm Staging; D025341:Principal Component Analysis; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D012007:Rectum / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor