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Prognostic impact of individual and complex mutations of the k-ras, p16 and p53 genes on postoperative prognosis and overall survival of patients with gastric cancer

Song Gun Kim, Chol Ryong Kwak, Song Ung Kang, Tae Yong Jon, Ke Ho Ju

Abstract


Background: The aim of this study was to determine the post-operative overall survival and prognostic factors associated with k-ras, p16, p53 gene mutations in patients with gastric cancer.

Materials: We used the paraffin-embedded specimens from 70 patients with gastric cancer who correspond with the investigation purpose (patients had performed D2 lymph node dissection, no pre and post-operation chemotherapy) from 2000 to 2015. The sample consisted of 49 (70.0%) males and 21 (30.0%) females.

Methods: The mutations of k-ras, p16 and p53 genes were assessed by polymerase chain reaction (PCR), PCR-single strand conformation polymorphism (PCR-SSCP).

Result: We studied complex mutation rates of these genes we detected that the complex mutation rate of k-ras and p16 with p53 no mutation was 10.0% (7/70) and post-operative overall survival time was 6.57±0.5 years, the complex mutation of p16 and p53 with no k-ras:10.0% (7/70), 1.57±0.5years, the complex mutation rate of k-ras and p53 with no p16: 18.6% (13/70), 6.29±0.5years, and the complex mutation rate of k-ras, p16 and p53 genes: 24.3% (17/70), 3.29±0.5years. No mutation rate :8.6%(6/70), 9.83±1.7 years.

Conclusion: The post-operative overall survival time depends on status of individual and complex mutations of p16 and p53 genes. In other words, we have found out that 5-year survival rate may be successfully high even though patients are in the last stage of gastric cancer if there are no complex mutations of these tumor suppress genes. Therefore, they can be used as the prognostic biomarker of gastric cancer.


Keywords


p16, k-ras, p53, gastric cancer, gene, mutation, pTNM stage, survival

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References


Anna Vilborg. et al. Regulation of tumor suppressor p53 at RNA level. Gastric Cancer. 2013; 88(7):645-652.

Atari J. Et al. K-ras mutations and cell kinetics in Helicobacter pylori associated gastric intestinal metaplasia. a comparison before and after eradication in patients with chronic gastritis and gastric cancer. J.Clin.Pathol. 2007; 60(8): 921-926.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin.2018; 68(6): 394–424.

Brenner H. et al.Epidemiology of stomach cancer. Methods Mol. Biol. 2009; 467–477,

Daniel C. Chung, Daniel A. Haber et al. Principles of Clinical Cancer Genetics: A Handbook from the Massachusetts General Hospita 2010; 47-60. Springer; 2010th edition (30 May 2010)

Ding Y. et al. Methylation and mutation analysis of p16 gene in gastric cancer. World J. Gastroenterol. 2003; 9(3): 423-426.

Dimosthenis E. Ziogas et al. Limitations of Isolated Tumor Cells in Gastric Cancer: Heterogeneity Requests Systems Biology Approaches Towards Personalized Medicine. Ann Surg Oncol. 2010; 17(1): 343–344.

Elena Miranda. et al. Genetic and Epigenetic Alterations in Primary Colorectal Cancers and Related Lymph Node and Liver Metastases. American Cancer Society. 2013; 119(2): 266-76.

Hiyama T. et al. The roles of H. pylori infection and K-ras gene mutation in gastric carcinogenesis. Nippon Rinsho. 2003: 61(1): 46-49.

Hitoshi Katai. et al. Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001–2007). Gastric Cancer. 2018; 21(1): 144–154.

Ichard M. Gore et al. Gastric Cancer. 2010; CAMBRIGE university press.7-10.

Igoer B. et al. The accuracy of sentinel node mapping according to T stage

in patients with gastric cancer. Gastric Cancer. 2010;13(1): 30-35.

Jemal A. et al. Cancer statistics, 2008. CA.Cancer J. Clin. 2008; 58(2): 71–96.

Jian-Xian Lin, Jacopo, Desiderio et al. Multicenter Validation Study of the American Joint Commission on Cancer (8th dition) for Gastric Cancer.Proposal for a Simplified and Improved TNM Staging System, journal of cancer. 2020; 11(12):3483-3491.

Jonine D. Figueroa et al. Cigarette smoking, body mass index, gastro-esophageal reflux disease, and non-steroidal anti-inflammatory drug use and risk of subtypes of esophageal and gastric cancers by P53 overexpression. Cancer Cause Control. 2009; 20(3):361-368.

Kazuhito Mita et al. Prognostic Factors Affecting Survival After Multivisceral Resection in Patients with Clinical T4b Gastric Cancer. J Gastrointest Surg. 2017; 21(12): 1993 – 1999.

K.-C. Lai et al. Association of genetic polymorphisms of MK, IL-4, p16, p21, p53 genes and human gastric cancer in Taiwan. EJSO. 2005; 31(10): 1135–1140.

Macdonald F. Et al. Molecular Biology of Cancer. BIOS Scientific Publi-shers. 2009; 140-170.

Mathijs P. Et al. Advances in Molecular Oncology. Spinger. 2007; 17-25.

Ming-Chung Jiang et al. “CSE1L modulates ras-induced cancer cell invasion: correlation of K-ras mutation and CSE1L expression in colorectal cancer progression”. The American Jouranl ofSurgery. 2013; 206(3): 418-427.

Niels Smakman, Inne H.M. Borel Rinkes, Emile E. Voest, et al. Control of colorectal metastasis formation by K-Ras. Biochimica et Biophysica Acta. 2005; 1756(2): 103 – 114.

Oki E. Et al. Genetic mutual relationship between PTEN and p53 In gastric cancer. Can-cer Letters. 2005; 227(1):33-38.

Olbert D. et al. The relation of p53 gene mutations to gastric cancer subsite and phenotype. Cancer Causes and Control. 1999;10(3): 227-231.

Yi Ding, et al. Methylation and mutation analysis of p16 gene in gastric cancer. World J Gastroenterol.2003 Mar;9(3):423-6. doi: 10.3748/wjg.v9.i3.423.

Ricardo Oliveros Wilches, Helena Facundo, Carlos Bonilla González, Ricardo Sánchez Pedraza et al. Case Report of Conversion Therapy in Stage IV Gastric Cancer. Rev Colomb Gastroenterol. 2018; 33 (1): DOI: http://dx.doi.org/10.22516/25007440.233

Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. Lancet. 2016; 388(10060):2654 –2664,

Wang M, Chen H, Wu K, Ding A, Zhang M, Zhang P, et al. Evaluation of the prognostic stage in the 8th edition of the American joint committee on Cancer in locally advanced breast cancer: an analysis based on SEER 18 database. Breast. 2018;37:56–63.

Xiaoying Wang Guofang Shu, Chanchan Gao et al. Electrochemical biosensor based on functional composite nanofibers for detection of K-ras gene via multiple signal amplification strategy. Analytical Biochemistry 2014; 466: 51–58.

Yeung-Leung Cheng Yeung-Leung Cheng, Shih-Chun Lee, Horng-Jyh Harn, Cheng-Jueng Chenet et al. Prognostic prediction of the immunohistochemical expression of p53 and p16 in resected non-small cell lung cancer. European Journal of Cardio-thoracic Surgery. 2003; 23(2): 221–228.

Y.-F Et al. Detection of circulating cancer cells with K-ras oncogene using membrane array. Cancer Letters 2005; 229(1): 115–122.

Ziyu Li, et al. Different prognostic implication of ypTNM stage and pTNM stage for gastric cancer: a propensity score-matched analysis. BMC Cancer. 2019; 19: 80.

Zuo Yunxia, Cao Jun, Zhu Guanshan et al. Mutations in epidermal growth factor receptor and K-ras in Chinese patients with colorectal cancer. BMC Medical Genetics. 2010; 11:34.

Tai Ma, Zhi-jun Wu, Hui Xu, Chang-hao Wu et al. Nomograms for predicting survival in patients with metastatic gastric adenocarcinoma who undergo palliative gastrectomy.BMC Cancer. 2019; 19: 852-860.




DOI: https://doi.org/10.37591/(rrjobi).v9i1.1253

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