title: Differential proteomic analysis of noncardia gastric cancer from individuals of northern Brazil.
abstract: Gastric cancer is the second leading cause of cancer-related death worldwide. The identification of new cancer biomarkers is necessary to reduce the mortality rates through the development of new screening assays and early diagnosis, as well as new target therapies. In this study, we performed a proteomic analysis of noncardia gastric neoplasias of individuals from Northern Brazil. The proteins were analyzed by two-dimensional electrophoresis and mass spectrometry. For the identification of differentially expressed proteins, we used statistical tests with bootstrapping resampling to control the type I error in the multiple comparison analyses. We identified 111 proteins involved in gastric carcinogenesis. The computational analysis revealed several proteins involved in the energy production processes and reinforced the Warburg effect in gastric cancer. ENO1 and HSPB1 expression were further evaluated. ENO1 was selected due to its role in aerobic glycolysis that may contribute to the Warburg effect. Although we observed two up-regulated spots of ENO1 in the proteomic analysis, the mean expression of ENO1 was reduced in gastric tumors by western blot. However, mean ENO1 expression seems to increase in more invasive tumors. This lack of correlation between proteomic and western blot analyses may be due to the presence of other ENO1 spots that present a slightly reduced expression, but with a high impact in the mean protein expression. In neoplasias, HSPB1 is induced by cellular stress to protect cells against apoptosis. In the present study, HSPB1 presented an elevated protein and mRNA expression in a subset of gastric cancer samples. However, no association was observed between HSPB1 expression and clinicopathological characteristics. Here, we identified several possible biomarkers of gastric cancer in individuals from Northern Brazil. These biomarkers may be useful for the assessment of prognosis and stratification for therapy if validated in larger clinical study sets.
authors.affiliation: Genetics Division, Department of Morphology and Genetic, Federal University of São Paulo, São Paulo, Brazil. mariana.morf@epm.br
authors.forename: Mariana Ferreira
authors.initials: MF
authors.lastname: Leal
authors.forename: Janete
authors.initials: J
authors.lastname: Chung
authors.forename: Danielle Queiroz
authors.initials: DQ
authors.lastname: Calcagno
authors.forename: Paulo Pimentel
authors.initials: PP
authors.lastname: Assumpção
authors.forename: Samia
authors.initials: S
authors.lastname: Demachki
authors.forename: Ismael Dale Cotrim Guerreiro
authors.initials: ID
authors.lastname: da Silva
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.forename: Rommel Rodríguez
authors.initials: RR
authors.lastname: Burbano
authors.forename: Marília
authors.initials: M
authors.lastname: de Arruda Cardoso Smith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001938:Brazil; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D040901:Proteomics; D021241:Spectrometry, Mass, Electrospray Ionization; D013274:Stomach Neoplasms / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase