title: Identification of pathways related to FAF1/H. pylori-associated gastric carcinogenesis through an integrated approach based on iTRAQ quantification and literature review.
abstract: Previously we showed that down-regulation of tumor suppressor FAF1 mRNA, potentially caused by H. pylori, correlated with increasing tumor differentiation and distant metastasis in gastric cancer. To identify molecular details about how FAF1 and H. pylori contribute to gastric carcinogenesis, we used the iTRAQ labeling approach involving LC-MS/MS to perform proteomic analysis of HGC-27 gastric cancer cells stably transfected with an FAF1 transgene and/or infected with H. pylori. Of the 2926 proteins examined, proteomics identified 157 for which the expression was altered as a result of FAF1 expression, 500 with altered expression as a result of H. pylori infection, and 246 with altered expression as a combined result of FAF1 expression and H. pylori infection. A literature review identified 21 proteins as being differentially expressed in H. pylori-associated gastric cancer in at least two studies. These two complementary analyses were combined in Ingenuity Pathway software, which predicted that FAF1/H. pylori-associated gastric carcinogenesis alters primarily biochemical pathways related to mitochondrial dysfunction, oxidative phosphorylation, integrin signaling, cholesterol/leucine metabolism and G2/M checkpoint regulation. Differential expression of key proteins in several of these pathways was validated by immunoblotting in HGC-27 cells. This integrated approach combining proteomics and literature searching may prove fruitful for elucidating how FAF1 expression and H. pylori infection affect gastric carcinogenesis.
  
  
  CONCLUSIONS
  We established, for the first time, the proteomics databases of gastric cancer cell HGC-27 overexpressing FAF1 and infected with H. pylori through an integrated approach based on iTRAQ quantification and literature review, this strategy responded to the call for greater focus on data integration in primary/previous proteomic studies; and provided an integrated picture of the reference pathways and networks behind FAF1/H. pylori-associated gastric carcinogenesis, particularly pathways of mitochondrial dysfunction, oxidative phosphorylation, integrin signaling, cholesterol/leucine metabolism and G2/M checkpoint regulation.
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China. Electronic address: gelianying2008@163.com.
authors.forename: Lianying
authors.initials: L
authors.lastname: Ge
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D008954:Models, Biological; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology*; D018511:Systems Integration; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C490780:FAF1 protein, human
keywords: FAF1; Gastric cancer; H. pylori; Pathway; Proteomics; iTRAQ