title: Proteomics-Based Identification and Analysis of Proteins Associated with Helicobacter pylori in Gastric Cancer.
abstract: Helicobacter pylori (H. pylori) is a spiral-shaped Gram-negative bacterium that causes the most common chronic infection in the human stomach. Approximately 1%-3% of infected individuals develop gastric cancer. However, the mechanisms by which H. pylori induces gastric cancer are not completely understood. The available evidence indicates a strong link between the virulence factor of H. pylori, cytotoxin-associated gene A (CagA), and gastric cancer. To further characterize H. pylori virulence, we established three cell lines by infecting the gastric cancer cell lines SGC-7901 and AGS with cagA+ H. pylori and transfecting SGC-7901 with a vector carrying the full-length cagA gene. We detected 135 differently expressed proteins from the three cell lines using proteome technology, and 10 differential proteins common to the three cell lines were selected and identified by LC-MS/MS as well as verified by western blot: β-actin, L-lactate dehydrogenase (LDH), dihydrolipoamide dehydrogenase (DLD), pre-mRNA-processing factor 19 homolog (PRPF19), ATP synthase, calmodulin (CaM), p64 CLCP, Ran-specific GTPase-activating protein (RanGAP), P43 and calreticulin. Detection of the expression of these proteins and genes encoding these proteins in human gastric cancer tissues by real-time PCR (RT-qPCR) and western blot revealed that the expression of β-ACTIN, LDH, DLD, PRPF19 and CaM genes were up-regulated and RanGAP was down-regulated in gastric cancer tissues and/or metastatic lymph nodes compared to peri-cancerous tissues. High gene expression was observed for H. pylori infection in gastric cancer tissues. Furthermore, the LDH, DLD and CaM genes were demethylated at the promoter -2325, -1885 and -276 sites, respectively, and the RanGAP gene was highly methylated at the promoter -570 and -170 sites in H. pylori-infected and cagA-overexpressing cells. These results provide new insights into the molecular pathogenesis and treatment targets for gastric cancer with H. pylori infection.
authors.affiliation: Molecular Biology Key Laboratory, Guizhou Medical University, Guiyang, Guizhou, China.|Department of Clinical Laboratory, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Jianjiang
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Guizhou Cancer Hospital, Guiyang, Guizhou, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Wang
authors.affiliation: Molecular Biology Key Laboratory, Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Molecular Biology Key Laboratory, Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Molecular Biology Key Laboratory, Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Molecular Biology Key Laboratory, Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xu
authors.affiliation: Molecular Biology Key Laboratory, Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Molecular Biology Key Laboratory, Guizhou Medical University, Guiyang, Guizhou, China.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Guan
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000382:microbiology / Q000556:secondary; D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism*; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome