Original Article

The Expression Analysis of MEST1 and GJA1 Genes in Gastric Cancer in Association with Clinicopathological Characteristics

Abstract

Gastric cancer is an invasive cancer, which is usually diagnosed in advanced stages. However, the markers affecting its progression, and invasion are of great importance in its diagnosis and treatment. The current research aimed to study the correlation of genes that contributed to epithelial-mesenchymal transition (EMT), Mest1, and GjA1, with some clinicopathological specifications in gastric cancer patients to better comprehend the functions of these genes in this tumor.

Materials and Methods: RNA was extracted from the tumor, and normal tissues and cDNA were synthesized. Then, by designing specific primers for Gja1 and Mest1 genes, their expressions were studied by RT-PCR. The data was analyzed by GraphPad Prism 8 software.

Results: Significant differences among the expressions of the mentioned genes associated with clinicopathological variables of gastric cancer patients, including tumor size, grade, stage, metastasis, and lymphatic invasion were seen.

Conclusion: The obtained data showed the important role of EMT-related genes, Gja1 and Mest1 in the clinical progression of the tumor. Further studies with larger sample sizes are required to confirm these genes as biomarker candidates for detecting gastric cancer.

1. Van Cutsem E, Sagaert X, Topal B, et al. Gastric cancer. Lancet. 2016;388(10060):2654-64.
2. Li H, Wei Z, Wang C, et al. Gender differences in gastric cancer survival: 99,922 cases based on the SEER database. J Gastrointest Surg. 2020;24(8):1747-57.
3. Pasechnikov V, Chukov S, Fedorov E, et al. Gastric cancer: prevention, screening and early diagnosis. World J Gastroenterol. 2014; 20(38):13842-62.
4. Diepenbruck M, Christofori G. Epithelial–mesenchymal transition (EMT) and metastasis: yes, no, maybe? Curr Opin Cell Biol. 2016;43:7-13.
5. Abolhassani A, Riazi GH, Azizi E, et al. FGF10: Type III Epithelial Mesenchymal Transition and Invasion in Breast Cancer Cell Lines. J Cancer. 2014;5(7):537-47.
6. Shirkoohi R. Epithelial mesenchymal transition from a natural gestational orchestration to a bizarre cancer disturbance. Cancer Sci. 2013;104(1):28-35.
7. Ghavami TST, Irani S, Mirfakhrai R, et al. Differential expression of Scinderin and Gelsolin in gastric cancer and comparison with clinical and morphological characteristics. EXCLI J. 2020;19:750-761.
8. Pedersen IS, Dervan PA, Broderick D, et al. Frequent loss of imprinting of PEG1/MEST in invasive breast cancer. Cancer Res. 1999;59(21):5449-51.
9. Nakanishi H, Suda T, Katoh M, et al. Loss of imprinting of PEG1/MEST in lung cancer cell lines. Oncol Rep. 2004;12(6):1273-8.
10. Sado T, Nakajima N, Tada M, et al. A Novel Mesoderm‐Specific cDNA Isolated from a Mouse Embryonal Carcinoma Cell Line: (embryonal carcinoma cell/cDNA/in situ hybridization/mesoderm/mouse embryo). Dev Growth Differ. 1993;35(5):551-560.
11. Puebla C, Cisterna BA, Salas DP, et al. Linoleic acid permeabilizes gastric epithelial cells by increasing connexin 43 levels in the cell membrane via a GPR40-and Akt-dependent mechanism. Biochim Biophys Acta. 2016;1861(5):439-48.
12. Santin AD, Zhan F, Bignotti E, et al. Gene expression profiles of primary HPV16-and HPV18-infected early stage cervical cancers and normal cervical epithelium: identification of novel candidate molecular markers for cervical cancer diagnosis and therapy. Virology. 2005;331(2):269-91.
13. Untergasser A, Cutcutache I, Koressaar T, et al. Primer3—new capabilities and interfaces. Nucleic Acids Res. 2012;40(15):e115.
14. Maes M, Cogliati B, Yanguas SC, et al. Roles of connexins and pannexins in digestive homeostasis. Cell Mol Life Sci. 2015;72(15):2809-21.
15. Yahiro K, Hirayama T, Moss J, et al. Helicobacter pylori VacA toxin causes cell death by inducing accumulation of cytoplasmic connexin 43. Cell Death Dis. 2015;6(11):e1971.
16. Lerotic I, Vukovic P, Hrabar D, et al. Expression of NEDD9 and connexin-43 in neoplastic and stromal cells of gastric adenocarcinoma. Bosn J Basic Med Sci. 2021;21(5):542-8.
17. Li CH, Hao ML, Sun Y, et al. Ultrastructure of gap junction and Cx43 expression in gastric cancer tissues of the patients. Arch Med Sci. 2020;16(2):352-8.
18. Liu D, Zhou H, Wu J, et al. Infection by Cx43 adenovirus increased chemotherapy sensitivity in human gastric cancer BGC-823 cells: not involving in induction of cell apoptosis. Gene. 2015;574(2):217-24.
19. Radin JN, González-Rivera C, Frick-Cheng AE, et al. Role of connexin 43 in Helicobacter pylori VacA-induced cell death. Infect Immun. 2014;82(1):423-32.
20. Tang B, Peng ZH, Yu PW, et al. Expression and significance of Cx43 and E-cadherin in gastric cancer and metastatic lymph nodes. Med Oncol. 2011;28(2):502-8.
21. Liu X, Furuya T, Li D, et al. Connexin 26 expression correlates with less aggressive phenotype of intestinal type-gastric carcinomas. Int J Mol Med. 2010;25(5):709-16.
22. Fares J, Fares MY, Khachfe HH, et al. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct Target Ther. 2020;5(1):28.
23. Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2(6):442-54.
24. Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008;14(6):818-29.
25. Fidler IJ, Poste G. The “seed and soil” hypothesis revisited. Lancet Oncol. 2008;9(8):808.
26. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420-8.
27. Nicolson GL, Dulski KM, Trosko JE. Loss of intercellular junctional communication correlates with metastatic potential in mammary adenocarcinoma cells. Proc Natl Acad Sci U S A. 1988;85(2):473-6.
28. Kamibayashi Y, Oyamada Y, Mori M, et al. Aberrant expression of gap junction proteins (connexins) is associated with tumor progression during multistage mouse skin carcinogenesis in vivo. Carcinogenesis. 1995;16(6):1287-97.
29. Kataoka H, Nakano S, Oshimura M, et al. S081 Loss of Imprinting of PEG1/MEST, IGF2 in Head and Neck Cancer. Arch Otolaryngol Head Neck Surg. 2006;132(8):857-858.
30. Arand M, Grant DF, Beetham JK, et al. Sequence similarity of mammalian epoxide hydrolases to the bacterial haloalkane dehalogenase and other related proteins: implication for the potential catalytic mechanism of enzymatic epoxide hydrolysis. FEBS Lett. 1994;338(3):251-6.
31. Wu JI, Wang LH. Emerging roles of gap junction proteins connexins in cancer metastasis, chemoresistance and clinical application. J Biomed Sci. 2019;26(1):8.
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IssueVol 18, No 1 (2024) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijhoscr.v18i1.14747
Keywords
Gene; Expression; Gastric; Cancer; Mest1; GjA1

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How to Cite
1.
Pourjamal N, Shirkohi R, Rohani E, Hashemi M. The Expression Analysis of MEST1 and GJA1 Genes in Gastric Cancer in Association with Clinicopathological Characteristics. Int J Hematol Oncol Stem Cell Res. 2024;18(1):83-91.