Evaluation of RAGE (Receptor for Advanced Glycation End-products) Expression in Gastric Carcinoma of Egyptian patients in Relation to Helicobacter pylori Infection
Keywords:
Gastric carcinoma, Helicobacter Pylori, RAGE
Abstract
Background: Gastric cancer is one of the most common malignancies and is the second most common cause of death from cancer worldwide. Gastric cancer is a multistep process that is regulated by intrinsic and extrinsic cellular signals. Extrinsic factors include molecular patterns that are derived from either pathogens or cellular damage, which can promote tumourigenesis. Helicobacter pylori plays an important role in the pathogenesis of chronic gastritis and gastric adenocarcinoma. Receptor for Advanced Glycation End products (RAGE) is a pattern recognition receptor that binds multiple ligands derived from a damaged cell environment, and plays a critical role in promoting the intestinal tumorigenesis. The over-expression of RAGE has been associated with increased invasiveness and metastasis generation in different types of cancer, including gastric cancer. Therefore, the aim of this study was to evaluate the expression of RAGE protein in gastric carcinomas either in cases associated with Helicobacter pylori (Hp) infection or not, so as to predict its value as a target for therapy.Methods: 51 endoscopic and 19 surgical gastric biopsies including cases of gastric carcinoma, intestinal metaplasia and chronic gastritis were histopathologically and immunohistochemically studied for RAGE expression and were statistically discussed. Result: RAGE was not expressed in any case of gastritis or signet-ring gastric carcinomas. The RAGE cellular expression parameters were correlated significantly with the stages of gastric adenocarcinoma and lymph node metastasis and non-significantly with the grade of neoplasia. Our results showed no significant correlation between RAGE expression and Hp infection, either in chronic gastritis or malignant cases.Conclusion: RAGE expression could be identified as a possible marker for target therapy in some types of gastric carcinoma, possibly to control its invasive and metastatic potential, however, its relation to Hp infection was not quite evident in our current study.References
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2. Heijmans J, Büller NV, Hoff E, Dihal AA, van der Poll T, van Zoelen MA, et al. Rage signalling promotes intestinal tumourigenesis. Oncogene 2013;32:1202-6
3. Morales M E, Rojas R A, Monasterio A V, González B I, Figueroa C I, Manques M B, Romero E J, Llanos L J, Valdés M E, Cofré L C. Expression of RAGE in Helicobacter pylori infested gastric biopsies. Rev Med Chil. 2013 Oct;141(10):1240-8.
4- O'Brien DP, Romero-Gallo J, Schneider BG, et al. Regulation of the Helicobacter pylori Cellular Receptor Decay-accelerating Factor. J Biol Chem 2008; v.283(35)
5. Kang R, Tang D, Schapiro NE, Livesey KM, Farkas A, Loughran P, et al. The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ. 2010;17:666-76
6- Sparvero LJ, Asafu-Adjei D, Kang R, et al., RAGE (Receptor for Advanced Glycation Endproducts), RAGE Ligands, and their role in Cancer and Inflammation J Transl Med. 2009; 7: 17.
7. Odenbreit S. Adherence properties of Helicobacter pylori: impact on pathogenesis and adaptation to the host, Int. J. Med. Microbiol. 2005; 295317-324.
8. Schmidt AM, Yan SD, Yan SF, Stern MD. The multiligand receptor RAGE is a progression factor amplifying immune and inflammatory responses, J. Clin. Invest. 2001; 108 949e955
9. Donato R. RAGE: a single receptor for several ligands and different cellular responses: the case of certain S100 proteins, Curr. Mol. Med. 7(2007) 711e724
10- Stolte M, Meining A. The updated Sydney system: classification and grading of gastritis as the basis of diagnosis and treatment. Can J Gastroenterol. 2001; 15 No 9,
11- Xu XC, Abuduhadeer X, Zhang WB, T. Li, Gao H, Wang YH. Knockdown of RAGE Inhibits Growth and Invasion of Gastric Cancer Cells. Published online (2013) Nov 18.
12- Gharbiah Population Based Cancer Registry, Egypt. Ministry of Health and Population. Cancer in Egypt, triennial report of 2000–2002. (2007). MOH: Tanta, Egypt.
13- Peek RM Jr, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer. 2002;2:28–37.
14- Brenner H, Rothenbacher D, Arndt V. Epidemiology of stomach cancer. Methods Mol Biol Clifton NJ, 2009;472:467–477
15- Asaka M, Kato M, Kudo M, et al. Atrophic changes of gastric mucosa are caused by Helicobacter pylori infection rather than aging: studies in asymptomatic Japanese adults. Helicobacter. 1996 ;1:52–56.
16- Bornschein J, Kandulski A, Selgrad M, Malfertheiner P. From gastric inflammation to gastric cancer. Dig Dis. 2010; 28 (4-5): 609-14.
17- Blakwill F, Montovani A. Inflammation and cancer: back to Virchow? Lancet. 2001; 237: 539-45.
18- Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008, 454, 436-44.
19- Rojas A, Figueroa H, Morales E. Fueling inflammation at tumor microenvironment: the role of multiligand / rage axis. Carcinogenesis .2010; 31: 334-41.
20- Riehl A, J Nemeth, Angel P, Hess J. The RAGE receptor: Bridging inflammation and cancer. Cell Communication and Signaling . 2009, 7: 12. Available at: www.biosignaling.com
21- Wang D, Li T, YeG, Shen Z, Hu Y, Mou T, et al. Overexpression of the Receptor for Advanced Glycation Endproducts (RAGE) Is Associated with Poor Prognosis in Gastric Cancer. PLoSONE10. 2015 ; 4.
22- Stolte, M, Eidt, S. Lymphoid follicles in antral mucosa: immune response to Campylobacter pylori J. Clin. Pathol. 1991: 42, 1269-1271
23- Kuniyasu H, Oue N, Wakikawa A, et al. Expression of receptors for advanced glycation end-products (RAGE) is closely associated with the invasive and metastatic activity of gastric cancer. The Journal of pathology. 2002;196(2):163–70.
24- QIu-Yu ZHANG, LIN-QING Wu, TAO ZHANG, YAN-FEI HAN, Xu LIN. Autophagy-mediated HMGB1 release promotes gastric cancercell survival via RAGE activation of extracellular signal-regulated kinases 1/2.ONCOLOGY REPORTS 2015; 33: 1630-1638
Published
2016-10-11
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