期刊论文详细信息
BMC Medical Genomics
Transcriptome signatures in Helicobacter pylori-infected mucosa identifies acidic mammalian chitinase loss as a corpus atrophy marker
Samuel B Lundin1  Jens Nielsen5  Sven Pettersson3  Henrik Sjövall4  Martin Lloyd Hibberd2  Shugui Wang3  Kuntal Worah1  Kaisa Thorell1  Intawat Nookaew5 
[1] Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Genome Institute of Singapore, Singapore, Singapore;Department of Microbiology and Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden;Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
关键词: Acidic mammalian chitinase;    Integrated analysis;    Gastric cancer;    Corpus gastritis;   
Others  :  1091754
DOI  :  10.1186/1755-8794-6-41
 received in 2013-04-19, accepted in 2013-10-01,  发布年份 2013
【 摘 要 】

Background

The majority of gastric cancer cases are believed to be caused by chronic infection with the bacterium Helicobacter pylori, and atrophic corpus gastritis is a predisposing condition to gastric cancer development. We aimed to increase understanding of the molecular details of atrophy by performing a global transcriptome analysis of stomach tissue.

Methods

Biopsies from patients with different stages of H. pylori infection were taken from both the antrum and corpus mucosa and analyzed on microarrays. The stages included patients without current H. pylori infection, H. pylori-infected without corpus atrophy and patients with current or past H. pylori-infection with corpus-predominant atrophic gastritis.

Results

Using clustering and integrated analysis, we found firm evidence for antralization of the corpus mucosa of atrophy patients. This antralization harbored gain of gastrin expression, as well as loss of expression of corpus-related genes, such as genes associated with acid production, energy metabolism and blood clotting. The analyses provided detailed molecular evidence for simultaneous intestinal metaplasia (IM) and spasmolytic polypeptide expressing metaplasia (SPEM) in atrophic corpus tissue. Finally, acidic mammalian chitinase, a chitin-degrading enzyme produced by chief cells, was shown to be strongly down-regulated in corpus atrophy.

Conclusions

Transcriptome analysis revealed several gene groups which are related to development of corpus atrophy, some of which were increased also in H. pylori-infected non-atrophic patients. Furthermore, loss of acidic chitinase expression is a promising marker for corpus atrophy.

【 授权许可】

   
2013 Nookaew et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Wroblewski LE, Peek RM Jr, Wilson KT: Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev 2010, 23(4):713-739.
  • [2]Peek RM Jr, Fiske C, Wilson KT: Role of innate immunity in Helicobacter pylori-induced gastric malignancy. Physiol Rev 2010, 90(3):831-858.
  • [3]Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010, 127(12):2893-2917.
  • [4]Mills JC, Shivdasani RA: Gastric epithelial stem cells. Gastroenterol 2011, 140(2):412-424.
  • [5]Nozaki K, Ogawa M, Williams JA, Lafleur BJ, Ng V, Drapkin RI, Mills JC, Konieczny SF, Nomura S, Goldenring JR: A molecular signature of gastric metaplasia arising in response to acute parietal cell loss. Gastroenterol 2008, 134(2):511-522.
  • [6]Goldenring JR, Nam KT, Wang TC, Mills JC, Wright NA: Spasmolytic polypeptide-expressing metaplasia and intestinal metaplasia: time for reevaluation of metaplasias and the origins of gastric cancer. Gastroenterol 2010, 138(7):2207-2210. 2210 e2201
  • [7]Du P, Kibbe WA, Lin SM: Lumi: a pipeline for processing Illumina microarray. Bioinforma 2008, 24(13):1547-1548.
  • [8]Smyth GK: Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 2004, 3(1):1544-6115.
  • [9]Patil KR, Nielsen J: Uncovering transcriptional regulation of metabolism by using metabolic network topology. Proc Natl Acad Sci USA 2005, 102(8):2685-2689.
  • [10]Oliveira AP, Patil KR, Nielsen J: Architecture of transcriptional regulatory circuits is knitted over the topology of bio-molecular interaction networks. BMC Syst Biol 2008, 2:17. BioMed Central Full Text
  • [11]Grotkjaer T, Winther O, Regenberg B, Nielsen J, Hansen LK: Robust multi-scale clustering of large DNA microarray datasets with the consensus algorithm. Bioinform 2006, 22(1):58-67.
  • [12]Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pages F, Trajanoski Z, Galon J: ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinform 2009, 25(8):1091-1093.
  • [13]Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003, 13(11):2498-2504.
  • [14]Workman C, Jensen LJ, Jarmer H, Berka R, Gautier L, Nielser HB, Saxild HH, Nielsen C, Brunak S, Knudsen S: A new non-linear normalization method for reducing variability in DNA microarray experiments. Genome Biol 2002, 3(9):research0048.1-0048.16.
  • [15]Hubbel E: Plier White Paper. California: Santa Clala; 2005.
  • [16]Lee HJ, Nam KT, Park HS, Kim MA, Lafleur BJ, Aburatani H, Yang HK, Kim WH, Goldenring JR: Gene expression profiling of metaplastic lineages identifies CDH17 as a prognostic marker in early stage gastric cancer. Gastroenterol 2010, 139(1):213-225. e213
  • [17]Rubie C, Kempf K, Hans J, Su T, Tilton B, Georg T, Brittner B, Ludwig B, Schilling M: Housekeeping gene variability in normal and cancerous colorectal, pancreatic, esophageal, gastric and hepatic tissues. Mol Cell Probes 2005, 19(2):101-109.
  • [18]Kubista M, Andrade JM, Bengtsson M, Forootan A, Jonak J, Lind K, Sindelka R, Sjoback R, Sjogreen B, Strombom L, et al.: The real-time polymerase chain reaction. Mol Aspects Med 2006, 27(2–3):95-125.
  • [19]Ponten F, Gry M, Fagerberg L, Lundberg E, Asplund A, Berglund L, Oksvold P, Bjorling E, Hober S, Kampf C, et al.: A global view of protein expression in human cells, tissues, and organs. Mol Syst Biol 2009, 5:337.
  • [20]Wen S, Felley CP, Bouzourene H, Reimers M, Michetti P, Pan-Hammarstrom Q: Inflammatory gene profiles in gastric mucosa during Helicobacter pylori infection in humans. J Immunol 2004, 172(4):2595-2606.
  • [21]Hofman VJ, Moreilhon C, Brest PD, Lassalle S, Le Brigand K, Sicard D, Raymond J, Lamarque D, Hebuterne XA, Mari B, et al.: Gene expression profiling in human gastric mucosa infected with Helicobacter pylori. Mod Pathol 2007, 20(9):974-989.
  • [22]Galamb O, Gyorffy B, Sipos F, Dinya E, Krenacs T, Berczi L, Szoke D, Spisak S, Solymosi N, Nemeth AM, et al.: Helicobacter pylori and antrum erosion-specific gene expression patterns: the discriminative role of CXCL13 and VCAM1 transcripts. Helicobacter 2008, 13(2):112-126.
  • [23]Gruno M, Peet N, Seppet E, Kadaja L, Paju K, Eimre M, Orlova E, Peetsalu M, Tein A, Soplepmann J, et al.: Oxidative phosphorylation and its coupling to mitochondrial creatine and adenylate kinases in human gastric mucosa. Am J Physiol Regul Integr Comp Physiol 2006, 291(4):R936-R946.
  • [24]Helander HF, Leth R, Olbe L: Stereological investigations on human gastric mucosa: I. Normal oxyntic mucosa. Anat Rec 1986, 216(3):373-380.
  • [25]Duman JG, Pathak NJ, Ladinsky MS, McDonald KL, Forte JG: Three-dimensional reconstruction of cytoplasmic membrane networks in parietal cells. J Cell Sci 2002, 115(Pt 6):1251-1258.
  • [26]Mills JC, Andersson N, Stappenbeck TS, Chen CC, Gordon JI: Molecular characterization of mouse gastric zymogenic cells. J Biol Chem 2003, 278(46):46138-46145.
  • [27]Menguy R, Desbaillets L, Masters YF: Mechanism of stress ulcer: influence of hypovolemic shock on energy metabolism in the gastric mucosa. Gastroenterol 1974, 66(1):46-55.
  • [28]Menguy R, Masters YF: Mechanism of stress ulcer. 3. Effects of hemorrhagic shock on energy metabolism in the mucosa of the antrum, corpus, and fundus of the rabbit stomach. Gastroenterol 1974, 66(6):1168-1176.
  • [29]Allen A, Sellers LA, Bennett MK: The gastric mucosal epithelial barrier: role of mucus and fibrin. Scand J Gastroenterol Suppl 1987, 128:6-13.
  • [30]Sorbye H, Ovrebo K, Gislason H, Kvinnsland S, Svanes K: Blood flow and mucoid cap protect against penetration of carcinogens into superficially injured gastric mucosa of rats. Dig Dis Sci 1995, 40(8):1720-1728.
  • [31]Xia HH, Kalantar JS, Talley NJ, Wyatt JM, Adams S, Chueng K, Mitchell HM: Antral-type mucosa in the gastric incisura, body, and fundus (antralization): a link between Helicobacter pylori infection and intestinal metaplasia? Am J Gastroenterol 2000, 95(1):114-121.
  • [32]Stemmermann GN: Intestinal metaplasia of the stomach. A status report. Cancer 1994, 74(2):556-564.
  • [33]Rubio CA, Jaramillo E, Suzuki G, Lagergren P, Nesi G: Antralization of the gastric mucosa of the incisura angularis and its gastrin expression. Int J Clin Exp Pathol 2009, 2(1):65-70.
  • [34]Schmidt PH, Lee JR, Joshi V, Playford RJ, Poulsom R, Wright NA, Goldenring JR: Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Lab Invest 1999, 79(6):639-646.
  • [35]Jae Huh W, Mysorekar IU, Mills JC: Inducible activation of Cre recombinase in adult mice causes gastric epithelial atrophy, metaplasia, and regenerative changes in the absence of "floxed" alleles. Am J Physiol Gastrointest Liver Physiol 2010, 299(2):G368-G380.
  • [36]Reddi AH: Interplay between bone morphogenetic proteins and cognate binding proteins in bone and cartilage development: noggin, chordin and DAN. Arthritis Res 2001, 3(1):1-5. BioMed Central Full Text
  • [37]Shinohara M, Mao M, Keeley TM, El-Zaatari M, Lee HJ, Eaton KA, Samuelson LC, Merchant JL, Goldenring JR, Todisco A: Bone morphogenetic protein signaling regulates gastric epithelial cell development and proliferation in mice. Gastroenterol 2010, 139(6):2050-2060. e2052
  • [38]Bleuming SA, He XC, Kodach LL, Hardwick JC, Koopman FA, Ten Kate FJ, van Deventer SJ, Hommes DW, Peppelenbosch MP, Offerhaus GJ, et al.: Bone morphogenetic protein signaling suppresses tumorigenesis at gastric epithelial transition zones in mice. Cancer Res 2007, 67(17):8149-8155.
  • [39]Suzuki M, Fujimoto W, Goto M, Morimatsu M, Syuto B, Iwanaga T: Cellular expression of gut chitinase mRNA in the gastrointestinal tract of mice and chickens. J Histochem Cytochem 2002, 50(8):1081-1089.
  • [40]Strobel S, Roswag A, Becker NI, Trenczek TE, Encarnacao JA: Insectivorous bats digest chitin in the stomach using acidic Mammalian chitinase. PLoS One 2013, 8(9):e72770.
  • [41]Ohno M, Togashi Y, Tsuda K, Okawa K, Kamaya M, Sakaguchi M, Sugahara Y, Oyama F: Quantification of Chitinase mRNA Levels in Human and Mouse Tissues by Real-Time PCR: Species-Specific Expression of Acidic Mammalian Chitinase in Stomach Tissues. PLoS One 2013, 8(6):e67399.
  • [42]Cozzarini E, Bellin M, Norberto L, Polese L, Musumeci S, Lanfranchi G, Paoletti MG: CHIT1 and AMCase expression in human gastric mucosa: correlation with inflammation and Helicobacter pylori infection. Eur J Gastroenterol Hepatol 2009, 21(10):1119-1126.
  • [43]Hartl D, He CH, Koller B, Da Silva CA, Kobayashi Y, Lee CG, Flavell RA, Elias JA: Acidic mammalian chitinase regulates epithelial cell apoptosis via a chitinolytic-independent mechanism. J Immunol 2009, 182(8):5098-5106.
  • [44]Lee CG, Da Silva CA, Dela Cruz CS, Ahangari F, Ma B, Kang MJ, He CH, Takyar S, Elias JA: Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury. Annu Rev Physiol 2011, 73:479-501.
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