title: Expression profile of malignant and nonmalignant lesions of esophagus and stomach: differential activity of functional modules related to inflammation and lipid metabolism.
abstract: Adenocarcinomas of stomach and esophagus are frequently associated with preceding inflammatory alterations of the normal mucosa. Whereas intestinal metaplasia of the gastric mucosa is associated with higher risk of malignization, Barrett's disease is a risk factor for adenocarcinoma of the esophagus. Barrett's disease is characterized by the substitution of the squamous mucosa of the esophagus by a columnar tissue classified histopathologically as intestinal metaplasia. Using cDNA microarrays, we determined the expression profile of normal gastric and esophageal mucosa as well as intestinal metaplasia and adenocarcinomas from both organs. Data were explored to define functional alterations related to the transformation from squamous to columnar epithelium and the malignant transformation from intestinal metaplasia to adenocarcinomas. Based on their expression profile, adenocarcinomas of the esophagus showed stronger correlation with intestinal metaplasia of the stomach than with Barrett's mucosa. Second, we identified two functional modules, lipid metabolism and cytokine, as being altered with higher statistical significance. Whereas the lipid metabolism module is active in samples representing intestinal metaplasia and inactive in adenocarcinomas, the cytokine module is inactive in samples representing normal esophagus and esophagitis. Using the concept of relevance networks, we determined the changes in linear correlation of genes pertaining to these two functional modules. Exploitation of the data presented herein will help in the precise molecular characterization of adenocarcinoma from the distal esophagus, avoiding the topographical and descriptive classification that is currently adopted, and help with the proper management of patients with Barrett's disease.
authors.affiliation: Ludwig Institute for Cancer Research, São Paulo, Brazil.
authors.forename: Luciana I
authors.initials: LI
authors.lastname: Gomes
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Esteves
authors.forename: Alex F
authors.initials: AF
authors.lastname: Carvalho
authors.forename: Elier B
authors.initials: EB
authors.lastname: Cristo
authors.forename: Roberto
authors.initials: R
authors.lastname: Hirata
authors.forename: Waleska K
authors.initials: WK
authors.lastname: Martins
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Marques
authors.forename: Luiz P
authors.initials: LP
authors.lastname: Camargo
authors.forename: Helena
authors.initials: H
authors.lastname: Brentani
authors.forename: Adriane
authors.initials: A
authors.lastname: Pelosof
authors.forename: Cláudia
authors.initials: C
authors.lastname: Zitron
authors.forename: Rubens A
authors.initials: RA
authors.lastname: Sallum
authors.forename: André
authors.initials: A
authors.lastname: Montagnini
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
authors.forename: E Jordão
authors.initials: EJ
authors.lastname: Neves
authors.forename: Luiz F L
authors.initials: LF
authors.lastname: Reis
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D020411:Oligonucleotide Array Sequence Analysis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines