title: The combined expression of metaplasia biomarkers predicts the prognosis of gastric cancer.
abstract: BACKGROUND
  Our previous study indicated that gene expression profiling of intestinal metaplasia (IM) or spasmolytic polypeptide-expressing metaplasia (SPEM) can identify useful prognostic markers of early-stage gastric cancer, and seven metaplasia biomarkers (MUC13, CDH17, OLFM4, KRT20, LGALS4, MUC5AC, and REG4) were selectively expressed in 17-50% of gastric cancer tissues. We investigated whether the combined expression of these metaplasia biomarkers could predict the prognosis of advanced stage gastric cancer.
  
  
  METHODS
  The expression of seven metaplasia biomarkers was evaluated immunohistochemically using tissue microarrays comprised of 450 gastric cancer patients. The clinicopathologic correlations and the prognostic impact were analyzed according to the expression of multiple biomarkers.
  
  
  RESULTS
  MUC13, CDH17, LGALS4, and REG4 were significant prognostic biomarkers in univariate analysis. No expression of four markers was found in 56 cases (14.2%); 1 marker was seen in 67 cases (17%), 2 in 106 cases (27%), 3 in 101 cases (25.7%), and 4 in 63 cases (16%). Patients in which two or fewer proteins were expressed (group B) showed younger age, undifferentiated or diffuse type cancer, larger tumor size, larger number of metastatic lymph nodes, and more advanced stage than those in which three or more proteins were expressed (group A). In undifferentiated or stage II/III gastric cancer, the prognosis of group B was significantly poorer than that of group A by multivariate analysis.
  
  
  CONCLUSIONS
  The combined loss of expression of multiple metaplasia biomarkers is considered an independent prognostic indicator in undifferentiated or stage II/III gastric cancer.
authors: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors: Yun-Suhk
authors: YS
authors: Suh
authors: Hyuk-Joon
authors: HJ
authors: Lee
authors: Eun-Jung
authors: EJ
authors: Jung
authors: Min-A
authors: MA
authors: Kim
authors: Ki Taek
authors: KT
authors: Nam
authors: James R
authors: JR
authors: Goldenring
authors: Han-Kwang
authors: HK
authors: Yang
authors: Woo Ho
authors: WH
authors: Kim
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis; D005260:Female; D037541:Galectin 4 / Q000032:analysis; D020869:Gene Expression Profiling; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D053554:Keratin-20 / Q000032:analysis; D037181:Lectins, C-Type / Q000032:analysis; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D055271:Mucin 5AC / Q000032:analysis; D009077:Mucins / Q000032:analysis; D009367:Neoplasm Staging; D000073718:Pancreatitis-Associated Proteins; D011379:Prognosis; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C490584:CDH17 protein, human; D015820:Cadherins; D037541:Galectin 4; C507499:KRT20 protein, human; D053554:Keratin-20; C511927:LGALS4 protein, human; D037181:Lectins, C-Type; C429552:MUC13 protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; C454127:OLFM4 protein, human; D000073718:Pancreatitis-Associated Proteins; C428528:REG4 protein, human; D016179:Granulocyte Colony-Stimulating Factor