title: Protein expression profiling and molecular classification of gastric cancer by the tissue array method.
abstract: OBJECTIVE
  Gastric cancer is heterogeneous clinically and histologically, and prognosis prediction by tumor grade or type is difficult. Although previous studies have suggested that frozen tissue-based molecular classifications effectively predict prognosis, prognostic classification on formalin-fixed tissue is needed, especially in early gastric cancer.
  
  
  METHODS
  We immunostained 659 consecutive gastric cancers using 56 tumor-associated antibodies and the tissue array method. Hierarchical cluster analyses were done before and after feature selection. To optimize classifier number and prediction accuracy for prognosis, a supervised analysis using a support vector machine algorithm was used.
  
  
  RESULTS
  Of 56 gene products, 27 survival-associated proteins were selected (feature selection), and hierarchical clustering identified two clusters: cluster 1 and cluster 2. Cluster 1 cancers were more likely to have intestinal type, earlier stage, and better prognosis than cluster 2 (P<0.05). In 187 early gastric cancers (pT1), cluster 2 was associated with the presence of metastatic lymph nodes (P=0.026). Kaplan-Meier survival curves stratified by pathologic tumor-lymph node metastasis revealed that cluster 2 was associated with poor prognosis in stage I or II cancer (P<0.05). Support vector machines and genetic algorithms selected nine classifiers from the whole data set, another nine classifiers for stage I and II, and eight classifiers for stage III and IV. The prediction accuracies for patient outcome were 73.1%, 88.1%, and 76%, respectively.
  
  
  CONCLUSIONS
  Protein expression profiling using the tissue array method provided a useful means for the molecular classification of gastric cancer into survival-predictive subgroups. The molecular classification predicted lymph node metastasis and prognosis in early stage gastric cancer.
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Gyeonggi, Seoul, Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Cho
authors.forename: Hee Eun
authors.initials: HE
authors.lastname: Lee
authors.forename: Min A
authors.initials: MA
authors.lastname: Kim
authors.forename: Ji Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Do Joong
authors.initials: DJ
authors.lastname: Park
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.forename: Byung Lan
authors.initials: BL
authors.lastname: Lee
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D004798:Enzymes / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
chemical_list: D004798:Enzymes; D009363:Neoplasm Proteins