title: Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening.
abstract: OBJECTIVE
  Improving methods for early detection of gastric cancer could reduce mortality. Measurements of serum pepsinogen levels have been used for screening in Japan without satisfactory levels of sensitivity or specificity. Trefoil factor family (TFF) proteins (TFF1, TFF2, and TFF3) are small and stable molecules secreted by the mammalian gastrointestinal tract. Foveolar hyperplasia, spasmolytic polypeptide (TFF2)-expressing metaplasia, and intestinal metaplasia are histologic changes observed in patients with atrophic gastritis; they express TFF1, TFF2, and TFF3, respectively. We investigated whether serum levels of TFF can be used as markers for gastric cancer screening.
  
  
  METHODS
  Serum was collected from 183 patients with gastric cancer and 280 healthy individuals without cancer. Serum levels of anti-Helicobacter pylori immunoglobulin G, pepsinogen I, pepsinogen II, TFF1, TFF2, and TFF3 were measured by enzyme-linked immunosorbent assay and associated with gastric cancer.
  
  
  RESULTS
  Using a cutoff of 3.6 ng/mL, the level of TFF3 was significantly increased in serum samples from patients with cancer (odds ratio, 18.1; 95% confidence interval, 11.2-29.2); using this test, patients with cancer were identified with 80.9% sensitivity and 81.0% specificity. The test for TFF3 had a significantly higher odds ratio than that for pepsinogen. A test for the combination of TFF3 and pepsinogen had better results than the test for only pepsinogen.
  
  
  CONCLUSIONS
  Serum levels of TFF3 are a better marker of gastric cancer than pepsinogen; a test for the combined levels of serum pepsinogen and TFF3 could improve gastric cancer screening.
authors.affiliation: Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Aikou
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Ohmoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Gunji
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Matsuhashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.forename: Hirona
authors.initials: H
authors.lastname: Miura
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kubota
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Yamagata
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Seto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.forename: James R
authors.initials: JR
authors.lastname: Goldenring
authors.forename: Michio
authors.initials: M
authors.lastname: Kaminishi
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Nomura
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods*; D016481:Helicobacter Infections / Q000097:blood; D016480:Helicobacter pylori; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood; D010455:Peptides / Q000097:blood*; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000097:blood* / Q000175:diagnosis*; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D010455:Peptides; C051838:TFF1 protein, human; C000604007:TFF2 protein, human; C082495:TFF3 protein, human; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins; D020116:Pepsinogen A