title: Lipid profiling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.
abstract: BACKGROUND
  Colorectal cancer (CRC) has attracted increasing attention due to its common occurrence and worldwide distribution.
  
  
  METHODS
  Direct-infusion positive and negative ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (DI-ESI(±)-FTICR MS) was applied to analyze the serum metabolites from 52 CRC patients and 52 healthy controls. Metabolites whose inter-group intensities were determined to be statistically significant by univariate and multivariate statistical analyses were further identified by a combination of the Human Metabolome Database, accurate mass measurement, isotopic abundance distribution simulation, and tandem mass spectrometry. Orthogonal partial least square discriminant analysis (OPLS-DA), based on the data from DI-ESI(±)-FTICR MS, revealed a remarkable discrimination among early stage patients, late stage patients, and healthy controls.
  
  
  RESULTS
  A total of 15 differentially expressed metabolites were identified and categorized into four lipid classes. Each lipid class demonstrated specific changing trends in CRC progression. Biomarker panel 1 containing palmitic amide, oleamide, hexadecanedioic acid, octadecanoic acid, eicosatrienoic acid, LPC(18:2), LPC(20:4), LPC(22:6), myristic acid and LPC(16:0) achieved excellent diagnostic accuracy with area under the ROC curve (AUC) of 0.991, a sensitivity of 0.981 and a specificity of 1.000 for differentiating early stage patients from healthy controls, which was better than the carcinoembryonic antigen biomarker.
  
  
  CONCLUSIONS
  Our study revealed that the consideration of CRC stages would be necessary in diagnostic biomarker discovery, as well as that attention should be paid to the facile loss of methyl chloride from the [M + Cl](-) form of LPC(16:0) in its tandem mass spectrum.
authors.affiliation: Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Xuzhen
authors.initials: X
authors.lastname: Qin
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Qiu
authors.forename: Yumei
authors.initials: Y
authors.lastname: Guo
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Chen
authors.forename: Gaoguang
authors.initials: G
authors.lastname: Song
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Fenjie
authors.initials: F
authors.lastname: Li
authors.forename: Shuai
authors.initials: S
authors.lastname: Guo
authors.forename: Baohua
authors.initials: B
authors.lastname: Wang
authors.forename: Zhili
authors.initials: Z
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism; D018450:Disease Progression; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D025341:Principal Component Analysis; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D008055:Lipids