title: Identification and assessment of new biomarkers for colorectal cancer with serum N-glycan profiling.
abstract: BACKGROUND
  The objectives of this study were to identify and validate the diagnostic value of N-glycan markers in colorectal cancer (CRC) and to uncover their underlying molecular mechanism.
  
  
  METHODS
  In total, 347 individuals, including patients with CRC, patients with colorectal adenoma, and healthy controls, were divided randomly into a training group (n = 287) and retrospective validation groups (n = 60). Serum N-glycan profiling was analyzed by DNA sequencer-assisted/flurophore-assisted carbohydrate electrophoresis (DSA-FACE). Two diagnostic models were constructed based on N-glycan profiling with logistic stepwise regression. The diagnostic performance of each model was assessed further in retrospective, prospective (n = 43), and follow-up (n = 46) cohorts. Lectin blot and reverse transcriptase-polymerase chain reaction were used to analyze the total core-fucosylated residues and molecular expression involved in core-fucosylation modifications in CRC.
  
  
  RESULTS
  Two diagnostic models designated CRCglycoA and CRCglycoB were constructed to differentiate CRC from normal and adenoma, respectively. The areas under the receiver operating characteristic curves (AUC) of both CRCglycoA and CRCglycoB were higher than the AUC of carcinoembryonic antigen (CEA) (CRCglycoA, 0.92 vs 0.81; CRCglycoB, 0.81 vs 0.73). The sensitivity and accuracy of CRCglycoA improved from 21.7% to 25% and from 11.63% to 18% in the training cohort, the retrospective cohort, and the prospective cohorts compared with the sensitivity and accuracy of CEA. The sensitivity of CRCglycoB improved from 20% to 28.23%. Both altered N-glycans, and results from the diagnostic models were reversed after curative surgery. The level of total core fucose residues and fucosyltransferase were decreased significantly in CRC.
  
  
  CONCLUSIONS
  The current results indicated that the N-glycan markers based diagnostic models are new, valuable, noninvasive alternatives for identifying CRC. The authors concluded that decreased fucosyltransferase may be responsible for decreased levels of total core-fucosylated modification in both tissues and serum from patients with CRC.
authors.affiliation: Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Zhao
authors.forename: Can-Ping
authors.initials: CP
authors.lastname: Ruan
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Zhi-Qian
authors.initials: ZQ
authors.lastname: Hu
authors.forename: Meng
authors.initials: M
authors.lastname: Fang
authors.forename: Xing
authors.initials: X
authors.lastname: Gu
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.forename: Jin-Yan
authors.initials: JY
authors.lastname: Zhao
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Gao
mesh_terms: D000236:Adenoma / Q000097:blood / Q000175:diagnosis*; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D037102:Lectins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D037102:Lectins; D011134:Polysaccharides