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Identification of protein expression signatures in gastric carcinomas using clustering analysis

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Begnami, Maria D. [1] ; Fregnani, Jose Humberto T. G. [2] ; Brentani, Helena [3] ; Torres, Cesar [4] ; Costa, Jr., Wilson Luiz [5] ; Montagnini, Andre [5] ; Nonogaki, Suely [1] ; Soares, Fernando A. [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] AC Camargo Hosp, Dept Pathol, Sao Paulo - Brazil
[2] Canc Hosp Barretos, Dept Gynecol, Barretos - Brazil
[3] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo - Brazil
[4] AC Camargo Hosp, Dept Med Arch & Stat, Sao Paulo - Brazil
[5] AC Camargo Hosp, Dept Abdominal Surg, Sao Paulo - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY; v. 27, n. 2, p. 378-384, FEB 2012.
Citações Web of Science: 5

Background and Aim: 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 e 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]-beta I, TGF-beta II, MutS homolog-2, bcl-2, bax, bak, bcl-x, adenomatous polyposis coli, clathrin, E-cadherin, beta-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. (AU)

Processo FAPESP: 98/14335-2 - Antonio Prudente Cancer Research Center
Beneficiário:Fernando Augusto Soares
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs