PROGNOSTIC VALUE OF REPRIMO METHYLATION IN PATIENTS WITH RESECTABLE GASTRIC CANCER
Abstract
The Reprimo gene methylation status is identified in primary tumors and peritoneal washings after radical surgical treatment of gastric cancer. The analysis allowed us to show a statistically significant change in the Reprimo status in peritoneal washings in patients before and after dissection (p = 0.007) and also to identify the conjugation of the Reprimo status in the primary tumor with the number of the metastatic lymph node pN (p = 0.043). The risk of disease progression with peritoneal dissemination and survival linked with the Reprimo tumor status, with the Reprimo status of peritoneal washings, and with lymph node metastases (pN) are identified using the multivariate analysis. The data allow us to consider the methylation status Reprimo as an additional indication for adjuvant intraperitoneal chemotherapy.
About the Authors
M. Yu. Reutovich
N. N. Alexandrov National Cancer Centre
Belarus
Ph. D. (Med.), Associate Professor.
Belarus
Ph. D. (Med.), Associate Professor.
A. I. Shmak
N. N. Alexandrov National Cancer Centre
Belarus
D. Sc. (Med.), Head of the Laboratory.
Belarus
D. Sc. (Med.), Head of the Laboratory.
O. V. Krasko
United Institute of Informatics Problems of the National Academy of Sciences of Belarus
Belarus
Ph. D. (Techn.), Associate Professor, Leading researcher.
Belarus
Ph. D. (Techn.), Associate Professor, Leading researcher.
R. M. Smolyakova
N. N. Alexandrov National Cancer Centre
Belarus
D. Sc. (Biol.), Associate Professor, Head of the Laboratory
Belarus
D. Sc. (Biol.), Associate Professor, Head of the Laboratory
A. S. Babenko
N. N. Alexandrov National Cancer Centre
Belarus
Ph. D. (Chem.), Head of the Department.
Belarus
Ph. D. (Chem.), Head of the Department.
References
1. Takahashi T., Suzuki M., Shigematsu H., Shivapurkar N., Echebiri C., Nomura M., Stastny V., Augustus M., Wu C. W., Wistuba I. I., Meltzer S. J., Gazdar A. F. “Aberrant methylation of Reprimo in human malignancies”, Inernational Journal of Cancer, 2005, vol. 115, pp. 503–510.
2. Saavedra K., Valbuena J., Olivares W., Marchant M. J., Rodríguez A., Torres-Estay V., Carrasco-Avino G., Guzmán L., Aguayo F., Carlos Roa J., Corvalán A. H. “Loss of Expression of Reprimo, a p53-induced Cell Cycle Arrest Gene, Correlates with Invasive Stage of Tumor Progression, p73 Expression in Gastric Cancer”, PLoS One, 2015, vol. 10 (5), pp. e0125834, Available at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0125834 (Accessed 08.05.2016).
3. Sato N., Fukushima N., Matsubayashi H., Iacobuzio-Donahue C. A., Yeo C. J., Goggins M. “Aberrant methylation of Reprimo correlates with genetic instability, predicts poor prognosis in pancreatic ductal adenocarcinoma”, Cancer, 2006, vol. 107, no. 2, pp. 251–257.
4. Clopper C. J., Pearson E. S. “The use of confidence or fiducial limits illustrated in the case of the binomial”, Biometrika, 1934, vol. 26, pp. 404–413.
5. “R Core Team (2016). “R: A language, environment for statistical computing. R Foundation for Statistical Computing”, Vienna, Austria, URL, Available at: https://www.R-project.org/ (Accessed 08.05.2016).
6. Therneau T. “A рackage for survival analysis in S_ version 2.38”, 2015, Available at: http://CRAN.R-project.org/package=survival> (Accessed 12.09.2016).
7. Fujiwara Y., Doki Y., Taniguchi H., Sohma I., Takiguchi S., Miyata H., Yamasaki M., Monden M. “Genetic detection of free cancer cells in the peritoneal cavity of the patient with gastric cancer: present status, future perspectives”, Gastric Cancer, 2007, vol. 10, pp. 197–204.
8. Ooki A., Yamashita K., Yamaguchi K., Mondal A., Nishimiya H., Watanabe M. “DNA damage-inducible gene, Reprimo functions as a tumor suppressor, is suppressed by promoter methylation in gastric cancer”, Molecular Cancer Research, 2013, vol. 11, no. 11, pp. 1362–1374.
9. Luo J., Zhu Y., Yang G., Gong L., Wang B., Liu H. “Loss of Reprimo, S100A2 expression in human gastric adenocarcinoma”, Diagnostic cytopathology, 2011, vol. 39, no. 10, pp. 752–757.
10. Marutsuka T., Shimada S., Shiomori K., Hayashi N., Yagi Y., Yamane T., Ogawa M. “Mechanisms of peritoneal metastasis after operation for non-serosa invasive gastric carcinoma: an ultrarapid detection system for intraperitoneal free cancer cells, a prophylactic strategy for peritoneal metastasis”, Clinical Cancer Research, 2003, vol. 9, no. 2, pp. 678–685.
11. Yokota T., Ishiyama S., Saito T., Teshima S., Narushima Y., Murata K., Iwamoto K., Yashima R., Yamauchi H., Kikuchi S. “Lymph node metastasis as a significant prognostic factor in gastric cancer: a multiple logistic regression analysis”, Scandinavian Journal of Gastroenterology, 2004, vol. 39, no. 4, pp. 380–384.
12. Kodera Y., Yamamura Y., Shimizu Y., Torii A., Hirai T., Yasui K., Morimoto T., Kato T. “Peritoneal washing cytology: prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection”, Journal of Surgical Oncology, 1999, vol. 72, pp. 60–65.
13. “Japanese Gastric Cancer Association Japanese classification of gastric carcinoma, 2nd English ed.”, Gastric Cancer, 2011, vol. 14, pp. 101–112.
14. Yano M., Yasuda T., Fujiwara Y., Takiguchi S., Miyata H., Monden M. “Preoperative intraperitoneal chemotherapy for patients with serosa-infiltrating gastric cancer”, Journal of Surgical Oncology, 2004, vol. 88, no. 1, pp. 39–43.
Review
For citations:
Reutovich M.Yu., Shmak A.I., Krasko O.V., Smolyakova R.M., Babenko A.S. PROGNOSTIC VALUE OF REPRIMO METHYLATION IN PATIENTS WITH RESECTABLE GASTRIC CANCER. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2017;(1):66-77. (In Russ.)
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