Kras Mutations and Egfr Expression as Prognostic and Predictive Factors in Cancer Patients
Main Article Content
Keywords
Cancer patients, Baghdad, K-ras, polymorphism, genotype, PCR.
Abstract
Cell proliferation is largely believed to be under the control of the epidermal growth factor receptor (EGFR), a member of the tyrosine kinase family of proteins. The existence of point mutations in the K-ras proto-oncogene, a member of the RAS gene family, is an essential determinant in cancer development. These alterations, which are involved in the control of signal transmission across the
plasma membrane, play a significant role in cancer development. Mutations in the K-ras gene are frequently discovered in pancreatic, lung, colon, and stomach cancer patients. K-ras mutations are most commonly seen in codons 12 and 13, with codon 61 being the least prevalent. This study examined the prognostic and predictive effect of EGFR expression and K-ras mutations in gastric cancer patients. The study group consisted of patients with stomach cancer who were followed up at Baghdad Teaching Hospital between March 2018 and April 2022. They were all diagnosed using paraffin blocks and slides. The Department of Pathology records at Baghdad Medical College in Iraq were searched for information on these patients' demographic and pathological characteristics and their survival rates. The immunohistochemistry method was utilised to examine the epidermal growth factor receptor (EGFR) expression in 62 patients' stomach tissues. The stomach tissues were paraffinfixed, and sections were cut from them. Mutagenic PCR and RFLP methods were used to investigate the occurrence of K-ras oncogene codon 12- and 13-point mutations. DNA was isolated from paraffin tissue samples acquired from EGFR-positive people. In 62 gastric cancer patients, the genotype frequencies of the K-ras gene codon 12 were determined to be 93.62 %, 6.38 %, and 0%, respectively. The genotype frequencies of the gene codon 13 were found to be 73.08 %, 26.02 %, and 0%, respectively. From previous studies it was clear that patients with wild-type K-ras polymorphism alleles responded favourably to Cetuximab and had their growth reduced. Individuals with these genotypes are also prevalent in our patient population. We have reason to believe that polymorphism research will be advantageous, notably in the treatment of personalised cancer care.
References
2. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359–86
3. J. Ferlay,M. Colombet,I. Soerjomataram,C. Mathers,D.M. Parkin,M. Piñeros,A. Znaor,F. Bray, Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods,Cancer Epidemiology,Volume144, Issue8, 2019,Pages 1941-1953
4. Wieduwilt MJ, Moasser MM. The epidermal growth factor receptor family: biology driving targeted therapeutics. Cell Mol Life Sci. 2008 May;65(10):1566-84. doi: 10.1007/s00018-008-7440-8. PMID: 18259690; PMCID: PMC3060045
5. Eric Bissada, Olivier Abboud, Zahi Abou Chacra, Louis Guertin, Xiaoduan Weng, Phuc Félix Nguyen-Tan, Jean-Claude Tabet, Ève Thibaudeau, Louise Lambert, Marie-Lise Audet, Bernard Fortin, Denis Soulières, "Prevalence of K-RAS Codons 12 and 13 Mutations in Locally Advanced Head and Neck Squamous Cell Carcinoma and Impact on Clinical Outcomes", International Journal of Otolaryngology, vol. 2013, Article ID 848021, 6 pages, 2013. https://doi.org/10.1155/2013/848021
6. Capellá, Gabriel & Cronauer-Mitra, Sandra & Pienado, M.A. & Perucho, Manuel. (1991). Frequency and Spectrum of Mutations at Codons 12 and 13 of the C-K-ras Gene in Human Tumors. Environmental health perspectives. 93. 125-31. 10.1289/ehp.9193125.
7. Brink, Mirian & Goeij, A.F.P.M. & Weijenberg, Matty & Roemen, Guido & Lentjes, Marjolein & Pachen, Marco & Smits, Kim & Bruïne, Adriaan & Goldbohm, R & Brandt, Piet. (2003). K-ras oncogene mutations in sporadic colorectal cancer in The Netherlands Cohort Study. Carcinogenesis. 24. 703-10. 10.1093/carcin/bgg009.
8. Cox AD, Der CJ. Ras history: The saga continues. Small GTPases. 2010 Jul;1(1):2-27. doi: 10.4161/sgtp.1.1.12178. PMID: 21686117; PMCID: PMC3109476.
9. Chang YS, Yeh KT, Hsu NC, Lin SH, Chang TJ, Chang JG. Detection of N-, H-, and KRAS codons 12, 13, and 61 mutations with universal RAS primer multiplex PCR and N-, H-, and KRAS-specific primer extension. Clin Biochem. 2010 Feb;43(3):296-301. doi:
10.1016/j.clinbiochem.2009.10.007. Epub 2009 Oct 29. PMID: 19879255.
10. Demir G, Ünsal D, Zengin N, Er Ö, Dane F, Yalçın Ş. Prognostic factors in 840 operated gastric cancer patients. TOG. Gastrointestinal Tumors Group Study, Medical Oncology Congress, Antalya; 2008,
11. Buğra D. Approach to early stage gastric cancer. Surgical principles and the situation in Turkey. Gastric Tumors Symposium, Istanbul, 17–18 December 2004
12. Meyers WC, Damiano RJ, Postlethwait, Rotolo FOR. Adenocarcinoma of the stomach. Ann urg. 1987, 205: 1-8.
13. SR Alberts, A Cervantes, CJH van de Velde. Gastric cancer: epidemiology, pathology and treatment. Annals of Oncology. 2003, 14 (Supplement 2): ii31-ii36.
14. Finkelstein SD, Sayegh R, Christensen S. Genotypic classification of colorectal adenocarcinoma. Cancer. 1993. 71: 3827-3838.
15. K Kimura, T Nagasaka, N Hoshizima, H Sasamoto, K Notohara, M Takeda, K Kominami, T Iishii, N Tanaka and N Matsubara. No Duplicate KRAS Mutation is Identified on the Same Allele in Gastric or Colorectal Cancer Cells with Multiple KRAS Mutations. The Journal of International Medical Research. 2007, 35: 450-457
16. H. Miki, M. Ohmori, AO Perantoni and T Enomoto. K-ras activation in gastric epithelial tumors in Japanese. Cancer letters. 1991. 58: 107-113.
17. Derek J. Jonker, Chris J. O’Callaghan, Christos S. Karapetis, John R. Zalcberg, Dongsheng Tu, Heather-Jane Au, Scott R. Berry, Marianne Krahn, Timothy Price, R. John Simes, Niall C. Tebbutt, Guy van Hazel, Rafal Wierzbicki, Christiane Langer and Malcolm J. Moore. Cetuximab for the Treatment of Colorectal Cancer. N Engl J Med. 2007. 357: 2040-2048.
18. Sebastian Stintzing, Volker Heinemann, Andreas Jung, Nicolas Moosmann, Wolfgang Hiddemann, Thomas Kirchner. The Treatment of Colorectal CancinomaWith Monoclonal Antibodies. Dtsch Arztebl Int. 2009, 106(12): 202–206.
19. Mahdi, E. M., & Mustafa, M. A. (2022). Effect of different concentrations of extract of Urtica dioica and Cladosporium cladosporiodes on Tribolium castaneum or: Coleoptera after 24-48 hours of exposure in Samarra City/Iraq. HIV Nursing, 22(2), 3207-3210.
20. Mustafa, M. A., Kadham, S. M., Abbass, N. K., Karupusamy, S., Jasim, H. Y., Alreda, B. A., ... & Ahmed, M. T. (2023). A novel fuzzy M-transform technique for sustainable ground water level prediction. Applied Geomatics, 1-7.
21. Kadham, S. M., Mustafa, M. A., Abbass, N. K., & Karupusamy, S. (2022). IoT and artificial intelligence–based fuzzy-integral N-transform for sustainable groundwater management. Applied Geomatics, 1-8.