title: Identification of protein expression signatures in gastric carcinomas using clustering analysis.
abstract: OBJECTIVE
  The identification of gastric carcinomas (GC) has traditionally been based on histomorphology. Recently, DNA microarrays have successfully been used to identify tumors through clustering of the expression profiles. Random forest clustering is widely used for tissue microarrays and other immunohistochemical data, because it handles highly-skewed tumor marker expressions well, and weighs the contribution of each marker according to its relatedness with other tumor markers. In the present study, we identified biologically- and clinically-meaningful groups of GC by hierarchical clustering analysis of immunohistochemical protein expression.
  
  
  METHODS
  We selected 28 proteins (p16, p27, p21, cyclin D1, cyclin A, cyclin B1, pRb, p53, c-met, c-erbB-2, vascular endothelial growth factor, transforming growth factor [TGF]-βI, TGF-βII, MutS homolog-2, bcl-2, bax, bak, bcl-x, adenomatous polyposis coli, clathrin, E-cadherin, β-catenin, mucin (MUC)1, MUC2, MUC5AC, MUC6, matrix metalloproteinase [MMP]-2, and MMP-9) to be investigated by immunohistochemistry in 482 GC. The analyses of the data were done using a random forest-clustering method.
  
  
  RESULTS
  Proteins related to cell cycle, growth factor, cell motility, cell adhesion, apoptosis, and matrix remodeling were highly expressed in GC. We identified protein expressions associated with poor survival in diffuse-type GC.
  
  
  CONCLUSIONS
  Based on the expression analysis of 28 proteins, we identified two groups of GC that could not be explained by any clinicopathological variables, and a subgroup of long-surviving diffuse-type GC patients with a distinct molecular profile. These results provide not only a new molecular basis for understanding the biological properties of GC, but also better prediction of survival than the classic pathological grouping.
authors.affiliation: Department of Pathology, A C Camargo Hospital, Sao Paulo, Brazil. mariadirlei@gmail.com
authors.forename: Maria D
authors.initials: MD
authors.lastname: Begnami
authors.forename: José Humberto T G
authors.initials: JH
authors.lastname: Fregnani
authors.forename: Helena
authors.initials: H
authors.lastname: Brentani
authors.forename: Cesar
authors.initials: C
authors.lastname: Torres
authors.forename: Wilson Luiz
authors.initials: WL
authors.lastname: Costa
authors.forename: Andre
authors.initials: A
authors.lastname: Montagnini
authors.forename: Suely
authors.initials: S
authors.lastname: Nonogaki
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001938:Brazil; D002277:Carcinoma / Q000737:chemistry* / Q000145:classification / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D016000:Cluster Analysis; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000145:classification / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins