Relationship between the Expression of the Thymidylate Synthase and the Prognosis of Gastric Cancer Patients Treated with Combinational Chemotherapy Regimen Including Fluorouracil, Docetaxel and Cisplatin
Background: Thymidylate synthase is one of the target enzymes of 5-fluorouracil. However, the clinical and prognostic significance of TS expression in gastric cancer has remained controversial. In this study, the expression of thymidylate synthase was evaluated in gastric cancer patients treated with combinational chemotherapy; moreover, the association between TS expression and clinicopathologic characteristics and overall survival of the patients were also assessed.
Materials and Methods: In this descriptive study, 89 pathological samples were gathered from patients at Kermanshah hospitals during 2008-2017. The survival status of patients was recorded and their overall survival was evaluated individually.
Results: The average survival period for low and high thymidylate synthase groups was 54 and 50 months, respectively, meaning higher survival time in the lower thymidylate group. But this difference was not statistically significant (log Rank=0.88). In addition, sex, stage, recurrence, and survival had no significant difference between the low and high expression of thymidylate synthase groups (p=0.89).
Conclusion: The results clearly indicated that the level of thymidylate synthase is not a significant modulator of 5- fluorouracil in gastric cancer patients. Nevertheless, evaluation of the level of the enzymes and markers, as well as their effects, is highly recommended for accurate selection of chemotherapeutical strategies.
2. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2020. CA Cancer J Clin. 2020; 70(1): 7-30.
3. Lichtenstein P, Holm NV, Verkasalo PK , et al. Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000; 13; 343(2):78-85.
4. Katherine D Crew , Alfred I Neugut. Epidemiology of gastric cancer. World J Gastroenterol. 2006; 12(3): 354–362.
5. M Inoue, S Tsugane. Epidemiology of gastric cancer in Japan. Postgrad Med J. 2004; 81(957): 419–24.
6. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87–108.
7. Orditura M, Galizia G, Sforza V, et al. Treatment of gastric cancer . World J Gastroenterol. 2014; 20 (7): 1635–49.
8. Tan YK, Fielding JW .Early diagnosis of gastric cancer. Eur J Gastroenterol Hepatol. 2006; 18(8):821-9.
9. Maskarinec G, Noh JJ .The effect of migration on cancer incidence among Japanese in Hawaii. Ethn Dis. (2004). 14:431–9
10. Atherton JC .The pathogenesis of helicobacter pylori-induced gastro-duodenal diseases. Annu Rev Pathol. 2006; 1:63–96.
11. Kusters JG, van Vliet AH, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev. 2006; 19(3):449–90.
12. Huang JQ, Sridhar S, Chen Y, et al. Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology. 1998; 114(6):1169-79.
13. Tsugane S, Sasazuki S. Diet and the risk of gastric cancer: review of epidemiological evidence. Gastric Cancer. , (2007). 10(2):75–83.
14. Blot WJ, Devesa SS, Kneller RW, et al. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA. 1991; 265(10):1287–9.
15. Chua YJ, Cunningham D. The UK NCRI MAGIC trial of perioperative chemotherapy in resectable gastric cancer: implications for clinical practice. Ann Surg Oncol. 2007; 14(10):2687-90.
16. Smalley SR, Benedetti JK, Haller DG, et al. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012; 30(19):2327–2333.
17. Aznab M, Beiki O, Pia KE, et al. Evaluation the Survival of Patients with Gastric Cancer Treated with Adjuvant or Palliative Chemotherapy. J Gastrointest Cancer. 2017; 48(1):31-37.
18. Verheij M, Jansen EPM, Cats A, et al. A multicenter randomized phase III trial of neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy in resectable gastric cancer: First results from the CRITICS study. J Clin Oncol. 2016; 35(15): suppl 4000-4000.
19. Longley DB, Harkin DP, Johnston PG .5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003; 3(5):330–8.
20. Papamichael D (2000). The Use of Thymidylate Synthase Inhibitors in the Treatment of Advanced Colorectal Cancer: Current Status. Oncologist. 1999; 4 (6): 478–87.
21. Peters GJ, Backus HH, Freemantle S, et al. Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. Biochim Biophys Acta. 2002; 1587 (2-3): 194–205.
22. Hadjipanayis A, Pantazi A, Potapova O. The Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014; 513(7517):202–209.
23. Cristescu R, Lee J, Nebozhyn M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015; 21(5):449-56.
24. Qianqian W, Ganglei L, Chunhong H. Molecular Classification of Gastric Adenocarcinoma. Gastroenterol Res. 2019; 12(6): 275–282.
25. Wu P, Wu D, Li L, et al. PD-L1 and Survival in Solid Tumors: A Meta-Analysis. PLoS One. 2015; 10(6):e0131403
26. Cavaliere A, Merz V , Casalino S , et al. Novel Biomarkers for Prediction of Response to Preoperative Systemic Therapies in Gastric Cancer. J Gastric Cancer. 2019; 19(4): 375–392.
27. De Vita F, Borg C, Farina G, et al. Ramucirumab and paclitaxel in patients with gastric cancer and prior trastuzumab: subgroup analysis from RAINBOW study. Future Oncol. 2019; 15 (23): 2723-2731.
28. Choi JH, Lim HY, Nam DK, et al. Expression of thymidylate synthase in gastric cancer patients treated with 5-fluorouracil and doxorubicin-based adjuvant chemotherapy after curative resection. Br J Cancer. 2001; 84(2):186–192.
29.Yeh CN, Jung SM, Chen TW, et al. Expression of thymidylate synthase determines the response of gastric cancer patients undergoing gastrectomy to 5-fluorouracil-based adjuvant chemotherapy. Langenbecks Arch Surg. 2010; 395(3):217-25.
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