Relationship between COX-2 expression and gastric carcinoma: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 ZHUO Qiang ¹ , NI Ma ¹ , YIBI Ranhen ¹ , JIANG Mingde ²

1. Department of Internal Medicine, Lasha People's Hospital, Lasha, 850000, P.R.China;
2. Department of Gastroenterology, Chengdu Military General Hospital, Chengdu, 610083, P.R.China;

Corresponding author：

ZHUO Qiang, Email: zhuoqiang2006@21cn.com

Keywords：

COX-2; Gastric carcinoma; Systematic review; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.201707010

Video：

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Objectives To evaluate the expression and clinical significance of COX-2 in gastric carcinoma. Methods Such databases as PubMed, CNKI, WanFang Data and VIP were searched for the studies on the association between COX-2 and gastric carcinoma from inception to January 2017. Two researchers independently screened literature, extracted data and evaluate the risk of bias of included studies. RevMan 5.3 software were used to analyze the data. Results Eleven case-control studies involving 1 366 patients were included. The results of meta-analysis showed that, there were significant differences of COX-2 expression in the following comparisons: gastric carcinoma vs. normal esophageal tissues (RR=1.69, 95%CI 1.39 to 2.06, P<0.000 01), with serosa invasivevs. without serosa invasive (RR=1.37, 95%CI 1.14 to 1.66, P=0.001), clinical stages Ⅰ-Ⅱ vs. clinical stages Ⅲ-Ⅳ (RR=0.78, 95%CI 0.69 to 0.90, P=0.000 3), as well as lymph node metastasis vs. non-lymph node metastasis (RR=1.48, 95%CI 1.34 to 1.63, P<0.000 01). While no significant difference was found between well/general differentiation group and poorly differentiation group (RR=0.84, 95%CI 0.51 to 1.38,P=0.48). Conclusion COX-2 expression is associated with depth of invasion, clinical stage and lymph node metastasis, which prompts that COX-2 may play an important role in the occurrence and development of gastric carcinoma. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.

Citation： ZHUO Qiang, NI Ma, YIBI Ranhen, JIANG Mingde. Relationship between COX-2 expression and gastric carcinoma: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2017, 17(11): 1276-1282. doi: 10.7507/1672-2531.201707010 Copy

1.	邹文斌, 李兆申. 中国胃癌发病率及死亡率研究进展. 中国实用内科杂志, 2014, 34(4): 408-413.
2.	Dubois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB J, 1998, 12(12): 1063-1073.
3.	Pang LY, Hurst EA, Argyle DJ. Cyclooxygenase-2: a role in cancer stem cell survival and repopulation of cancer cells during therapy. Stem Cells Int, 2016, 2016: 2048731.
4.	Yun CT, Yu HT, Min JT, et al. Notch2-induced COX-2 expression enhancing gastric cancer progression. Mol Carcinog, 2012, 51(12): 939-951.
5.	Wells GA, Shea B, O’connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non randomized studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
6.	丁涤非, 胡凯, 方萍. 胃癌组织中COX-2与PTEN的表达及临床病理的关系. 淮海医药, 2015, 33(5): 417-419.
7.	Yu JR, Wu YJ, Qin Q, et al. Expression of cyclooxygenase-2 in gastric cancer and its relation to liver metastasis and long-term prognosis. Word J Gastroenterol, 2005, 11(31): 4908-4911.
8.	Joo YE, Chung LJ, Park YK, et al. Expression of Cyclooxygenase-2, p53 and Ki-67 in Gastric Cancer. J Korean Med Sci, 2006, 21(5): 871-876.
9.	Okano H, Shinohara H, Miyamoto A, et al. Concomitant overexpression of cyclooxygenase-2 in her-2-positive on smad4-reduced human gastric carcinomas is associated with a poor patient outcome. Clin Cancer Res, 2004, 21(8): 6938-6945.
10.	Sonoda R, Naomoto Y, Shirakawa, et al. Preferential up-regulation of heparanase and cyclooxygenase-2 in carcinogenesis of Barrett’s oesophagus and intestinal-type gastric carcinoma. Histopathology, 2010, 57(1): 90-100.
11.	Uefuji K, Ichikura T, Mochizuki H. Increased expression of interleukin-1α and cyclooxygenase-2 in human gastric cancer: a possible role in tumor progression. Anticancer Res, 2005, 25(5): 3225-3230.
12.	Rehab M, Asmaa G, Moshira M, et al. Cyclooxygenase-2 expression in chronic gastritis and gastric carcinoma, correlation with prognostic parameters. J Egypt Natl Canc Inst, 2006, 18(4): 363-374.
13.	朱艳丽, 刘亮, 张天英. COX-2和C-MYC在胃癌发生发展中的表达及其相关性研究. 黑龙江医药科学, 2016, 39(5): 28-31.
14.	Salem MN, Elghany MEA, Lashin HE, et al. Expression of COX 2 in gastric mucosa of patients with gastric carcinoma and its correlation with the disease progression. J Am Sci, 2014, 10(9): 218-224.
15.	翟俊山, 李楠, 宋久刚. 胃癌组织中APPL1和COX-2的表达及其与患者预后的关系. 胃肠病学和肝病学杂志, 2016, 25(1): 16-19.
16.	Park ES, Do IG, Park CK, et al. Cyclooxygenase-2 is an independent prognostic factor in gastric carcinoma patients receiving adjuvant chemotherapy and is not associated with EBV infection. Clin Cancer Res, 2009, 15(1): 291-298.
17.	李红刚, 喻伦银, 刘铭球. 环氧化酶-2与肿瘤. 国外医学肿瘤学分册, 2001, 28(6). 420-423.
18.	Akhtar M, Cheng Y, Magno RM, et al. Promoter methylation regulates helicobacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells. Cancer Res, 2001, 61(6): 2399-2401.
19.	Saukkonen K, Buskens CJ, Sivula A, et al. COX-2 in cancer. Milestones in Drug Therapy, 2004, 11(3): 227-243.
20.	Khan Z, Khan N, Tiwari RP, et al. Biology of Cox-2: an application in cancer therapeutics. Curr Drug Targets, 2011, 12(7): 1082-1093.
21.	Nunez F, Bravo S, Cruzat F, et al. Wnt/β-catenin signaling enhances cyclooxygenase-2 (COX2) transcriptional activity in gastric cancer cells. Plos One, 2011, 6(4): 1-10.
22.	Tsujii M, Kwawano S, Tsujis, et al. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell, 1998, 93(5): 705-716.
23.	Yanislav K, Hiroyuki U, Satoru I, et al. Prognostic significance of VEGF expression in correlation with COX-2, microvessel density, and clinicopathological characteristics in human gastric carcinoma. Ann Surg Oncol, 2007, 14(10): 2738-2747.
24.	Robert A, Soslow MD, Andrew J, et al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer, 2000, 89(12): 2637-2645.
25.	Singh B, Berry JA, Shoher A, et al. COX-2 overexpression increases motility and invasion of breast cancer cells. Int J Oncol, 2005, 26(5): 1393-1399.
26.	Yan WF, Sun PC, Nie CF, et al. Cyclooxygenase-2 polymorphisms were associated with the risk of gastric cancer: evidence from a meta-analysis based on case-control studies. Tumour Biol, 2013, 34(6): 3323-3330.
27.	伊正辉. 胃癌组织中COX-2表达的Meta分析. 中国肿瘤, 2007, 16(5): 365-367.
28.	曾金燕. 胃癌组织中COX-2的表达及其与淋巴结转移相关性的Meta分析. 肿瘤防治研究, 2011, 38(5): 584-587.
29.	Hsu KW, Hsieh RH, Wu CW, et al. MBP-1 suppresses growth and metastasis of gastric cancer cells through COX-2. Mol Biol Cell, 2009, 20(24): 5127-5137.
30.	Yao LP, Liu F, Liu H, et al. The function and mechanism of COX-2 in angiogenesis of gastric cancer cells. J Exp Clin Cancer, 2011, 30(13): 1-5.

1. 邹文斌, 李兆申. 中国胃癌发病率及死亡率研究进展. 中国实用内科杂志, 2014, 34(4): 408-413.
2. Dubois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB J, 1998, 12(12): 1063-1073.
3. Pang LY, Hurst EA, Argyle DJ. Cyclooxygenase-2: a role in cancer stem cell survival and repopulation of cancer cells during therapy. Stem Cells Int, 2016, 2016: 2048731.
4. Yun CT, Yu HT, Min JT, et al. Notch2-induced COX-2 expression enhancing gastric cancer progression. Mol Carcinog, 2012, 51(12): 939-951.
5. Wells GA, Shea B, O’connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non randomized studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
6. 丁涤非, 胡凯, 方萍. 胃癌组织中COX-2与PTEN的表达及临床病理的关系. 淮海医药, 2015, 33(5): 417-419.
7. Yu JR, Wu YJ, Qin Q, et al. Expression of cyclooxygenase-2 in gastric cancer and its relation to liver metastasis and long-term prognosis. Word J Gastroenterol, 2005, 11(31): 4908-4911.
8. Joo YE, Chung LJ, Park YK, et al. Expression of Cyclooxygenase-2, p53 and Ki-67 in Gastric Cancer. J Korean Med Sci, 2006, 21(5): 871-876.
9. Okano H, Shinohara H, Miyamoto A, et al. Concomitant overexpression of cyclooxygenase-2 in her-2-positive on smad4-reduced human gastric carcinomas is associated with a poor patient outcome. Clin Cancer Res, 2004, 21(8): 6938-6945.
10. Sonoda R, Naomoto Y, Shirakawa, et al. Preferential up-regulation of heparanase and cyclooxygenase-2 in carcinogenesis of Barrett’s oesophagus and intestinal-type gastric carcinoma. Histopathology, 2010, 57(1): 90-100.
11. Uefuji K, Ichikura T, Mochizuki H. Increased expression of interleukin-1α and cyclooxygenase-2 in human gastric cancer: a possible role in tumor progression. Anticancer Res, 2005, 25(5): 3225-3230.
12. Rehab M, Asmaa G, Moshira M, et al. Cyclooxygenase-2 expression in chronic gastritis and gastric carcinoma, correlation with prognostic parameters. J Egypt Natl Canc Inst, 2006, 18(4): 363-374.
13. 朱艳丽, 刘亮, 张天英. COX-2和C-MYC在胃癌发生发展中的表达及其相关性研究. 黑龙江医药科学, 2016, 39(5): 28-31.
14. Salem MN, Elghany MEA, Lashin HE, et al. Expression of COX 2 in gastric mucosa of patients with gastric carcinoma and its correlation with the disease progression. J Am Sci, 2014, 10(9): 218-224.
15. 翟俊山, 李楠, 宋久刚. 胃癌组织中APPL1和COX-2的表达及其与患者预后的关系. 胃肠病学和肝病学杂志, 2016, 25(1): 16-19.
16. Park ES, Do IG, Park CK, et al. Cyclooxygenase-2 is an independent prognostic factor in gastric carcinoma patients receiving adjuvant chemotherapy and is not associated with EBV infection. Clin Cancer Res, 2009, 15(1): 291-298.
17. 李红刚, 喻伦银, 刘铭球. 环氧化酶-2与肿瘤. 国外医学肿瘤学分册, 2001, 28(6). 420-423.
18. Akhtar M, Cheng Y, Magno RM, et al. Promoter methylation regulates helicobacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells. Cancer Res, 2001, 61(6): 2399-2401.
19. Saukkonen K, Buskens CJ, Sivula A, et al. COX-2 in cancer. Milestones in Drug Therapy, 2004, 11(3): 227-243.
20. Khan Z, Khan N, Tiwari RP, et al. Biology of Cox-2: an application in cancer therapeutics. Curr Drug Targets, 2011, 12(7): 1082-1093.
21. Nunez F, Bravo S, Cruzat F, et al. Wnt/β-catenin signaling enhances cyclooxygenase-2 (COX2) transcriptional activity in gastric cancer cells. Plos One, 2011, 6(4): 1-10.
22. Tsujii M, Kwawano S, Tsujis, et al. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell, 1998, 93(5): 705-716.
23. Yanislav K, Hiroyuki U, Satoru I, et al. Prognostic significance of VEGF expression in correlation with COX-2, microvessel density, and clinicopathological characteristics in human gastric carcinoma. Ann Surg Oncol, 2007, 14(10): 2738-2747.
24. Robert A, Soslow MD, Andrew J, et al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer, 2000, 89(12): 2637-2645.
25. Singh B, Berry JA, Shoher A, et al. COX-2 overexpression increases motility and invasion of breast cancer cells. Int J Oncol, 2005, 26(5): 1393-1399.
26. Yan WF, Sun PC, Nie CF, et al. Cyclooxygenase-2 polymorphisms were associated with the risk of gastric cancer: evidence from a meta-analysis based on case-control studies. Tumour Biol, 2013, 34(6): 3323-3330.
27. 伊正辉. 胃癌组织中COX-2表达的Meta分析. 中国肿瘤, 2007, 16(5): 365-367.
28. 曾金燕. 胃癌组织中COX-2的表达及其与淋巴结转移相关性的Meta分析. 肿瘤防治研究, 2011, 38(5): 584-587.
29. Hsu KW, Hsieh RH, Wu CW, et al. MBP-1 suppresses growth and metastasis of gastric cancer cells through COX-2. Mol Biol Cell, 2009, 20(24): 5127-5137.
30. Yao LP, Liu F, Liu H, et al. The function and mechanism of COX-2 in angiogenesis of gastric cancer cells. J Exp Clin Cancer, 2011, 30(13): 1-5.

Chinese Journal of Evidence-Based Medicine

Relationship between COX-2 expression and gastric carcinoma: a meta-analysis

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