Volume 9, Issue 4 (Autumn 2020)                   J Occup Health Epidemiol 2020, 9(4): 194-205 | Back to browse issues page

XML Print

1- MSc in Clinical Biochemistry, Dept. of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
2- Assistant Prof., Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
3- Associate Prof., Dept. of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
4- Assistant Prof., Dept. of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
5- Associate Prof., Dept. of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
6- Prof., Dept. of Clinical Biochemistry, Afzalipoor Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. , mahmoodies@yahoo.com
Article history
Received: 2020/08/17
Accepted: 2021/01/30
ePublished: 2021/06/21
Subject: Epidemiology
Abstract:   (1061 Views)

Background: Characterization of genes and precise assessment of the number of copies are crucial for understanding the basis of emergence, progression, and identification of predictive markers of tumor malignancy. This study aimed to investigate the role of the changes in some central genes in gastric cancer.
Materials and Methods: In this experimental study, 30 patients with gastric surgery were selected by random sampling from four hospitals in Kerman to investigate BAX, BCL-2, P53, and MICAL-2 genes in cancerous and healthy tissues. They were then studied using real-time RT-qPCR, PCR- SSCP, and sequencing.
Results: Demographic analysis demonstrated that 66.6% of patients with gastric cancer were men. The age range of men and women was 26-93 and 33-83 years, respectively. In terms of tumor pathology, there was 93.3% adenocarcinoma, 6.6% gastrointestinal stromal tumor (GIST), 16.6% intestinal type, 10% diffuse type, and 73.3% unknown type. The two exons of the p53 gene showed a 2.04 and 3.81 fold increase in expression relative to normal adjacent tissue. Results showed the upregulation of Bcl-2 (1.54%) and MICAL2 (2.23%), while the expression of Bax was downregulated (0.87%). Bcl-2/Bax ratio was not solely correlated with the progression and clinical outcome of gastric cancer.
Conclusion: The data suggest that the changes in BAX, BCL2, P53, and MICAL-2 genes play a key role in gastric cancer.

Keywords: BAX [MeSH], BCL2 [MeSH], P53 [MeSH], MICAL-2 [MeSH], Sequencing [MeSH], Gene [MeSH]
Full-Text [PDF 894 kb]   (482 Downloads) |   |   Full-Text (HTML)  (307 Views)  

1. Weinberg R. The biology of cancer. 2nd ed. New York, United States: w. w. norton & company;; 2013.
2. Xu Gf, Zhang WJ, Sun Q, Xu X, Zou X, Guan W. Combined epithelial-mesenchymal transition with cancer stem cell-like marker as predictors of recurrence after radical resection for gastric cancer. World J Surg Oncol 2014; 12:368. [DOI] [PMID] [PMCID]
3. Kanda M, Kodera Y. Recent advances in the molecular diagnostics of gastric cancer. World J Gastroenterol 2015; 21(34):9838. [DOI] [PMID] [PMCID]
4. Malekzadeh R, Derakhshan MH, Malekzadeh Z. Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med 2009; 12(6):576-83. [PMID]
5. Lajus TB, Sales RM. CDH1 germ-line missense mutation identified by multigene sequencing in a family with no history of diffuse gastric cancer. Gene 2015; 568(2):215-9. [DOI] [PMID]
6. De Vries AC, Kuipers EJ. Review article: Helicobacter pylori eradication for the prevention of gastric cancer. Aliment Pharmacol Ther 2007; 26 Suppl 2:25-35. [DOI] [PMID]
7. Yu Q. Restoring p53-mediated apoptosis in cancer cells: new opportunities for cancer therapy. Drug Resist Updat 2006; 9(1-2):19-25. [DOI] [PMID]
8. Mirmajidi SH, Ataee R, Barzegar A, Nikbakhsh N, Shaterpour M. Low Expression of the bcl2 Gene in Gastric Adenocarcinomas in Mazandaran Province of Iran. Asian Pac J Cancer Prev 2015; 16(14):6067-71. [DOI] [PMID]
9. Zhao D, Tahaney WM, Mazumdar A, Savage MI, Brown PH. Molecularly targeted therapies for p53-mutant cancers. Cell Mol Life Sci 2017; 74(22):4171-87. [DOI] [PMID] [PMCID]
10. Motalleb G, Sancholi S, Yegane Moghadam A, Talaee R. P53 gene expression evaluation in patients with esophageal cancer using reverse transcriptase real time polymerase chain reaction. Pajoohandeh 2015; 20(3):154-62. [Article]
11. Meng L, Lin L, Zhang H, Nassiri M, Morales AR, Nadji M. Multiple mutations of the p53 gene in human mammary carcinoma. Mutat Res 1999; 435(3):263-9. [DOI] [PMID]
12. Shiao YH, Rugge M, Correa P, Lehmann HP, Scheer WD. P53 alteration in gastric precancerous lesions. Am J Pathol 1994; 144(3):511-7. [PMID] [PMCID]
13. Mariotti S, Barravecchia I, Vindigni C, Pucci A, Balsamo M, Libro R, et al. MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transition involved in cancer growth and invasion. Oncotarget 2016; 7(2):1808-25. [DOI] [PMID] [PMCID]
14. Vanoni MA. Structure-function studies of MICAL, the unusual multidomain flavoenzyme involved in actin cytoskeleton dynamics. Arch Biochem Biophys 2017; 632:118-41. [DOI] [PMID]
15. Zhou Y, Gunput RA, Adolfs Y, Pasterkamp RJ. MICALs in control of the cytoskeleton, exocytosis, and cell death. Cell Mol Life Sci 2011; 68(24):4033-44. [DOI] [PMID] [PMCID]
16. Ashida S, Furihata M, Katagiri T, Tamura K, Anazawa Y, Yoshioka H, et al. Expression of novel molecules, MICAL2-PV (MICAL2 prostate cancer variants), increases with high Gleason score and prostate cancer progression. Clin Cancer Res 2006; 12(9):2767-73. [DOI] [PMID]
17. Zhou Y, Li Y, Zheng J, Liu K, Zhang H. Detecting of gastric cancer by Bcl-2 and Ki67. Int J Clin Exp Pathol 2015; 8(6):7287. [PMID] [PMCID]
18. Karimabad MN, Mahmoodi M, Jafarzadeh A, Darehkordi A, Hajizadeh MR, Khorramdelazad H, et al. The novel Indole-3-formaldehyde (2-AITFEI-3-F) is involved in processes of apoptosis induction? Life Sci 2017; 181:31-44. [DOI] [PMID]
19. Ruijter JM, Ramakers C, Hoogaars WM, Karlen Y, Bakker O, van den Hoff MJ, et al. Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res 2009; 37(6):e45. [DOI] [PMID] [PMCID]
20. Uchino S, Noguchi M, Ochiai A, Saito T, Kobayashi M, Hirohashi S. p53 mutation in gastric cancer: a genetic model for carcinogenesis is common to gastric and colorectal cancer. Int J Cancer 1993; 54(5):759-64. [DOI] [PMID]
21. Abbasi M, Mobaien A, Majlesi A, Kamalian N, Monsef A. A Survey of p53 and HER-2/neu Over Expression in Patients with Gastric Cancer and Correlation with Prognosis. Avicenna Journal of Clinical Medicine 2008; 15(3):5-10. [Article]
22. Golmohamadi R, Nikbakht M, Salehi M, Mokhtari M. Detection of P53 exon 6 mutions in colorectal cancer patients by PCR-SSCP method in Isfahan Hospital during 2004-2005. Feyz 2006; 10(2):1-6. [Article]
23. Maehara Y, Tomoda M, Hasuda S, Kabashima A, Tokunaga E, Kakeji Y, et al. Prognostic value of p53 protein expression for patients with gastric cancer- - a multivariate analysis. Br J Cancer 1999; 79(7-8):1255-61. [DOI] [PMID] [PMCID]
24. Joshaghani HR, Koochaki E, Amini R, Derakhshandeh P, Ehsani A, Shabani M, et al. Determination of P53 gene mutations in gastric cancer by PCR-SSCP. Journal of Gorgan University of Medical Sciences 2003; 5(2):36-42. [Article]
25. Luinetti O, Fiocca R, Villani L, Alberizzi P, Ranzani GN, Solcia E. Genetic pattern, histological structure, and cellular phenotype in early and advanced gastric cancers: evidence for structure-related genetic subsets and for loss of glandular structure during progression of some tumors. Hum Pathol 1998; 29(7):702-9. [DOI] [PMID]
26. Honda T, Tamura G, Endoh Y, Nishizuka S, Kawata S, Motoyama T. Expression of tumor suppressor and tumor-related proteins in differentiated carcinoma, undifferentiated carcinoma with tubular component and pure undifferentiated carcinoma of the stomach. Jap J Clin Oncol 2005; 35(10):580-6. [DOI] [PMID]
27. Yamashita K, Yoshida T, Shinoda H, Okayasu I. Novel method for simultaneous analysis of p53 and K-ras mutations and p53 protein expression in single histologic sections. Arch Pathol Lab Med 2001; 125(3):347-52. [DOI] [PMID]
28. Leahy DT, Salman R, Mulcahy H, Sheahan K, O'Donoghue DP, Parfrey NA. Prognostic significance of p53 abnormalities in colorectal carcinoma detected by PCR–SSCP and immunohistochemical analysis. J Pathol 1996; 180(4):364-70. [DOI] [PubMed]
29. Colomer A, Erill N, Verdú M, Roman R, Vidal A, Cordon-Cardo C, et al. Lack of p53 nuclear immunostaining is not indicative of absence of TP53 gene mutations in colorectal adenocarcinomas. Appl Immunohistochem Mol Morphol 2003; 11(2):130-7. [DOI] [PMID]
30. Koshida Y, Saegusa M, Okayasu I. Apoptosis, cell proliferation and expression of Bcl-2 and Bax in gastric carcinomas: immunohistochemical and clinicopathological study. Br J Cancer 1997; 75(3):367-73. [DOI] [PMID] [PMCID]
31. Mrozek A, Petrowsky H, Sturm I, Kraus J, Hermann S, Hauptmann S, et al. Combined p53/Bax mutation results in extremely poor prognosis in gastric carcinoma with low microsatellite instability. Cell Death Differ 2003; 10(4):461-7. [DOI] [PMID]
32. Taylor AC, Schuster K, McKenzie PP, Harris LC. Differential cooperation of oncogenes with p53 and Bax to induce apoptosis in rhabdomyosarcoma. Mol Cancer 2006; 5:53. [DOI] [PMID] [PMCID]
33. Lima VP, de Lima MA, André AR, Ferreira MV, Barros MA, Rabenhorst SH. H pylori (CagA) and Epstein-Barr virus infection in gastric carcinomas: correlation with p53 mutation and c-Myc, Bcl-2 and Bax expression. World J Gastroenterol 2008; 14(6):884-91. [DOI] [PMID] [PMCID]
34. Gryko M, Pryczynicz A, Zareba K, Kędra B, Kemona A, Guzińska-Ustymowicz K. The expression of Bcl-2 and BID in gastric cancer cells. J Immunol Res 2014; 2014:953203. [DOI] [PMID] [PMCID]
35. Ho JR, Chapeaublanc E, Kirkwood L, Nicolle R, Benhamou S, Lebret T, et al. Deregulation of Rab and Rab effector genes in bladder cancer. PloS One 2012; 7(6):e39469. [DOI] [PMID] [PMCID]
36. Jalali Nadoushan MR, Davati A, Tavakoli A. Expression of Bcl-2 Gene in Primary Breast Cancer and its Correlation with Some Prognostic Factors. Journal of Mazandaran University of Medical Sciences 2007; 17(58):30-6. [Article]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.