Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 33093
Down-Regulated Gene Expression of GKN1 and GKN2 as Diagnostic Markers for Gastric Cancer
Authors: Amer A. Hasan, Mehri Igci, Ersin Borazan, Rozhgar A. Khailany, Emine Bayraktar, Ahmet Arslan
Abstract:
Gastric Cancer (GC) has high morbidity and fatality rate in various countries. It is still one of the most frequent and deadly diseases. Gastrokine1 (GKN1) and gastrokine2 (GKN2) genes are highly expressed in the normal stomach epithelium and play important roles in maintaining the integrity and homeostasis of stomach mucosal epithelial cells. In this study, 47 paired samples that were grouped according to the types of gastric cancer and the clinical characteristics of the patients, including gender and average of age. They were investigated with gene expression analysis and mutation screening by monitoring RT-PCR, SSCP and nucleotide sequencing techniques. Both GKN1 and GKN2 genes were observed significantly reduced found by (Wilcoxon signed rank test; p<0.05). As a result of gene screening, no mutation (no different genotype) was detected. It is considered that gene mutations are not the cause of gastrokines inactivation. In conclusion, the mRNA expression level of GKN1 and GKN2 genes statistically was decreased regardless the gender, age, or cancer type of patients. Reduced of gastrokine genes seem to occur at the initial steps of gastric cancer development.Keywords: Diagnostic biomarker, gastric cancer, nucleotide sequencing, semi-quantitative RT-PCR.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1110297
Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 1464References:
[1] F. Kamangar, G.M. Dores, and W.F. Anderson, “Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world” Journal of Clinical Oncology, vol. 24(14), pp. 2137-2150, 2006.
[2] R. Siegel, D. Naishadham, and A. Jemal, “Cancer statistics”, 2012. CA Cancer Journal Clinical, vol. 62(1), pp. 10-29, 2012.
[3] K.D. Crew, and A.I. Neugut, “Epidemiology of gastric cancer” World Journal Gastroenterol, vol. 12(3), pp. 354-362, 2006.
[4] B.J. Dicken, D.L. Bigam, C. Cass, J.R. Mackey, A. Joy, and S.M. Hamilton, “Gastric adenocarcinoma review and considerations for future directions” Ann Surg, vol. 241(1), pp. 27-39, 2005.
[5] C. K. Oine, Gastric cancer, 2nd edition, Weliy, New york, 2007; ch. 4, pp. 64-711.
[6] D.M. Roder, “The epidemiology of gastric cancer” Journal of Gastroetestinal, vol. 51, pp. 5-11, 2002.
[7] J.J. Du, K.F. Dou, S.Y. Peng, W.Z. Wang, Z.H. Wang, H.S. Xiao, W.X. Guan, Y.B. Liu, and Z.Q. GAO, “Down-regulated full-length novel gene GDDR and its effect on gastric cancer” Clinical surgery, vol. 83(13), pp. 1166-1168, 2003.
[8] Y. Yoshikawa, H. Mukai, F. Hino, K. Asada, and I. Kato, “Isolation of two novel genes, downregulated in gastric cancer” Japan Journal of Cancer Reseach, vol. 91(5), pp. 459-463, 2000.
[9] K.A. Oien, F. Gregor, S. Butler, R.K. Ferrier, I. Downie, Bryce, S. Burns, and W.N. Keith, “Gastrokine 1 is abundantly and specifically expressed in superficial gastric epithelium, down-regulated in gastric carcinoma, and shows high evolutionary conservation” Journal Pathol, vol. 203(3), pp. 789-797, 2004.
[10] J.H. Yoon, H. Song, C .Zhang, M .Jin, Y.H. Kang, S.W. Nam, J.Y. Lee, and W.S. Park. “Inactivation of the Gastrokine 1 gene in gastric adenomas and carcinomas” Journal of Pathology, vol. 223(5), pp. 618- 625, 2011.
[11] I. Kouznetsova, W. Laubinger, H. Kalbacher, T. Kalinski, F. Meyer, A. Roessner, and W. Hoffmann, “Biosynthesis of gastrokine-2 in the human gastric mucosa: restricted spatial expression along the antral gland axis and differential interaction with TFF1, TFF2 and mucins” Journal of Cell Physiology and Biochemistry, vol. 20(6), pp. 899-908, 2007.
[12] Y. Z. Igci, A. Arslan, E. Akarsu, S. Erkilic, M. Igci, S. Oztuzcu, B. Cengiz, B. Gogebakan, E. A. Cakmak, and A. T. Demiryurek, “Differential Expression of a Set of Genes in Follicular and Classic Variants of Papillary Thyroid Carcinoma‖” Endocr Pathol, vol. 2,(22), pp. 86-96, 2011.
[13] G.R. Yan, S.H. Xu, Z.L. Tan, and X.F. Yin, “Proteomics characterization of gastrokine 1-induced growth inhibition of gastric cancer cells” Proteomics, vol. 11(18), pp. 3657-3664, 2011.
[14] W. Mao, J. Chen, T.L. Peng, X.F. Yin, L.Z. Chen, and M.H. Chen. “Dow-nregulation of gastrokine-1 in gastric cancer tissues and restoration of its expression induced gastric cancer cells to apoptosis” Journal of Experimental Clinical Cancer Research, vol. 23 pp. 31-49, 2012.
[15] G. Chu, S. Qi, G. Yang, K. Dou, J. Du, and Z. Lu, “Gastrointestinal tract specific gene GDDR inhibits the progression of gastric cancer in a TFF1 dependent manner” Molecular Cell Biochemistry, vol. 359, pp. 369 374, 2012.
[16] S.F. Moss, J.W. Lee, E. Sabo, A.K. Rubin, J. Rommel, B.R. Westley, F.E. May, J. Gao, P.A. Meitner, R. Tavares, and M.B, Resnick. “Decreased expression of gastrokine 1 and the trefoil factor interactin protein TFIZ1/GKN2 in gastric cancer: influence of tumor histology and relationship to prognosis” Clinical Cancer Res, vol. 14(13), pp. 4161- 4167,2008.
[17] T.R. Menheniott, B. Kurklu, A.S. Giraud, “Gastrokines: stomachspecific proteins with putative homeostatic and tumor suppressor roles” American Journal of Physiology Gastrointestinal Liver Physiol, vol. 304(2), pp.109-121, 2013.
[18] O. Kim, J.H. Yoon, W.S. Choi, H. Ashktorab, D.T. Smoot, S.W. Nam, J.Y. Lee, and W.S. Park, “GKN2 Contributes to the Homeostasis of Gastric Mucosa by Inhibiting GKN1 Activity” Journal of Cell Physiol, vol. 229(6), pp. 762-771, 2014.
[19] J.H. Yoon, Y.J. Choi, W.S. Choi, H. Ashktorab, D.T. Smoot, S.W. Nam, J.Y. Lee, and W.S. Park, “GKN1- miR-185-DNMT1 axis suppresses gastric carcinogenesis through regulation of epigenetic alteration and cell cycle” Clinical Cancer Res, vol. 19(17), pp. 4599-4610, 2013.