title: The identification and characterization of novel N-glycan-based biomarkers in gastric cancer.
abstract: OBJECTIVE
  To identify and validate N-glycan biomarkers in gastric cancer (GC) and to elucidate their underlying molecular mechanism of action.
  
  
  METHODS
  In total, 347 individuals, including patients with GC (gastric cancer) or atrophic gastritis and healthy controls, were randomly divided into a training group (n=287) and a retrospective validation group (n=60). Serum N-glycan profiling was achieved with DNA sequencer-assisted/fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Two diagnostic models were constructed based on the N-glycan profiles using logistic stepwise regression. The diagnostic performance of each model was assessed in retrospective, prospective (n=60), and follow-up (n=40) cohorts. Lectin blotting was performed to determine total core-fucosylation, and the expression of genes involved in core-fucosylation in GC was analyzed by reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  We identified at least 9 N-glycan structures (peaks) and the levels of core fucose residues and fucosyltransferase were significantly decreased in GC. Two diagnostic models, designated GCglycoA and GCglycoB, were constructed to differentiate GC from control and atrophic gastritis. The areas under the receiver operating characteristic (ROC) curves (AUC) for both GCglycoA and GCglycoB were higher than those for CEA, CA19-9, CA125 and CA72-4. Compared with CEA, CA19-9, CA125 and CA72-4, the sensitivity of GCglycoA increased 29.66%, 37.28%, 56.78% and 61.86%, respectively, and the accuracy increased 10.62%, 16.82%, 25.67% and 28.76%, respectively. For GCglycoB, the sensitivity increased 27.97%, 35.59%, 55.09% and 60.17% and the accuracy increased 21.26%, 24.64%, 31.40% and 34.30% compared with CEA, CA19-9, CA125 and CA72-4, respectively. After curative surgery, the core fucosylated peak (peak 3) and the total core fucosylated N-glycans (sumfuc) were reversed.
  
  
  CONCLUSIONS
  The results indicated that the diagnostic models based on N-glycan markers are valuable and noninvasive alternatives for identifying GC. We concluded that decreased core-fucosylation in both tissue and serum from GC patients may result from the decreased expression of fucosyltransferase.
authors.affiliation: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Long
authors.initials: L
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.forename: Junlong
authors.initials: J
authors.lastname: Huang
authors.forename: Qunhao
authors.initials: Q
authors.lastname: Gu
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Fang
authors.forename: Jianpeng
authors.initials: J
authors.lastname: Jiao
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yue
mesh_terms: D015415:Biomarkers / Q000097:blood*; D005260:Female; D005757:Gastritis, Atrophic / Q000097:blood / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D061212:Memory, Episodic; D008875:Middle Aged; D011134:Polysaccharides / Q000097:blood* / Q000378:metabolism; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000097:blood* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011134:Polysaccharides