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Tumor Biology

, Volume 35, Issue 10, pp 10301–10307 | Cite as

Prognostic significance of cyclooxygenase-2 protein in pancreatic cancer: a meta-analysis

  • Di Wang
  • Xiao-Zhong Guo
  • Hong-Yu Li
  • Jia-Jun Zhao
  • Xiao-Dong Shao
  • Chun-Yan Wu
Research Article

Abstract

We conducted a meta-analysis of relevant cohort studies to investigate the relationships between cyclooxygenase-2 (COX-2) protein and the prognosis of pancreatic cancer. The following electronic databases were searched without language restrictions: MEDLINE (1966∼2013), the Library Database (Issue 12, 2013), EMBASE (1980∼2013), CINAHL (1982∼2013), Web of Science (1945∼2013), and the Chinese Biomedical Database (CBM) (1982∼2013). Meta-analysis was performed using the STATA statistical software. Six cohort studies with a total of 712 pancreatic cancer patients were involved in this meta-analysis. Our findings showed that COX-2-positive patients were significantly associated with a shorter overall survival (OS) than COX-2-negative patients (hazard ratio (HR) = 1.48, 95 % confidence interval (95%CI) = 1.12∼1.85, P < 0.001). A subgroup analysis by ethnicity also revealed that pancreatic cancer patients with an abnormal COX-2 expression exhibited a worse OS than COX-2-negative patients among both Asians and Caucasians (Asians: HR = 1.40, 95%CI = −0.09∼2.89, P = 0.066; Caucasians: HR = 1.49, 95%CI = 1.11∼1.87, P < 0.001, respectively). Our findings provide empirical evidence that abnormal COX-2 expression may be strongly correlated with poor prognosis for patients with pancreatic cancer. Thus, COX-2 protein may be a useful biomarker for pancreatic cancer.

Keywords

Cyclooxygenase-2 Pancreatic cancer Prognosis Meta-analysis 

Notes

Acknowledgments

We would like to acknowledge the reviewers for their helpful comments on this paper.

Conflicts of interest

None.

References

  1. 1.
    Ilic M, Vlajinac H, Marinkovic J, Kocev N. Pancreatic cancer mortality in Serbia from 1991-2010—a joinpoint analysis. Croat Med J. 2013;54(4):369–75.PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Chakraborty S, Baine MJ, Sasson AR, Batra SK. Current status of molecular markers for early detection of sporadic pancreatic cancer. Biochim Biophys Acta. 2011;1815(1):44–64.PubMedCentralPubMedGoogle Scholar
  3. 3.
    Krejs GJ. Pancreatic cancer: epidemiology and risk factors. Dig Dis. 2010;28(2):355–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Chu D, Kohlmann W, Adler DG. Identification and screening of individuals at increased risk for pancreatic cancer with emphasis on known environmental and genetic factors and hereditary syndromes. JOP. 2010;11(3):203–12.PubMedGoogle Scholar
  5. 5.
    Pandol S, Gukovskaya A, Edderkaoui M, Dawson D, Eibl G, Lugea A. Epidemiology, risk factors, and the promotion of pancreatic cancer: role of the stellate cell. J Gastroenterol Hepatol. 2012;27 Suppl 2:127–34.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Reid-Lombardo KM, Fridley BL, Bamlet WR, Cunningham JM, Sarr MG, Petersen GM. Inflammation-related gene variants as risk factors for pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2011;20(6):1251–4.PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Balkwill FR, Mantovani A. Cancer-related inflammation: common themes and therapeutic opportunities. Semin Cancer Biol. 2012;22(1):33–40.CrossRefPubMedGoogle Scholar
  8. 8.
    Blackford A, Serrano OK, Wolfgang CL, Parmigiani G, Jones S, Zhang X, et al. SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clin Cancer Res. 2009;15(14):4674–9.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Kirane A, Toombs JE, Ostapoff K, Carbon JG, Zaknoen S, Braunfeld J, et al. Apricoxib, a novel inhibitor of COX-2, markedly improves standard therapy response in molecularly defined models of pancreatic cancer. Clin Cancer Res. 2012;18(18):5031–42.PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Zhang H, Xu Y, Zhang Z, Liu R, Ma B. Association between COX-2 rs2745557 polymorphism and prostate cancer risk: a systematic review and meta-analysis. BMC Immunol. 2012;13:14.PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Ozhan G, Lochan R, Leathart JB, Charnley R, Daly AK. Cyclooxygenase-2 polymorphisms and pancreatic cancer susceptibility. Pancreas. 2011;40(8):1289–94.CrossRefPubMedGoogle Scholar
  12. 12.
    Wang R, Wang X, Lin F, Gao P, Dong K, Zhang HZ. shRNA-targeted cyclooxygenase (COX)-2 inhibits proliferation, reduces invasion and enhances chemosensitivity in laryngeal carcinoma cells. Mol Cell Biochem. 2008;317(1-2):179–88.CrossRefPubMedGoogle Scholar
  13. 13.
    Zidar N, Odar K, Glavac D, Jerse M, Zupanc T, Stajer D. Cyclooxygenase in normal human tissues–is COX-1 really a constitutive isoform, and COX-2 an inducible isoform? J Cell Mol Med. 2009;13(9B):3753–63.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Khan Z, Khan N, Tiwari RP, Sah NK, Prasad GB, Bisen PS. Biology of Cox-2: an application in cancer therapeutics. Curr Drug Targets. 2011;12(7):1082–93.CrossRefPubMedGoogle Scholar
  15. 15.
    Lau MT, Wong AS, Leung PC. Gonadotropins induce tumor cell migration and invasion by increasing cyclooxygenases expression and prostaglandin E(2) production in human ovarian cancer cells. Endocrinology. 2010;151(7):2985–93.CrossRefPubMedGoogle Scholar
  16. 16.
    Gangwar R, Mandhani A, Mittal RD. Functional polymorphisms of cyclooxygenase-2 (COX-2) gene and risk for urinary bladder cancer in North India. Surgery. 2011;149(1):126–34.CrossRefPubMedGoogle Scholar
  17. 17.
    Hill R, Li Y, Tran LM, Dry S, Calvopina JH, Garcia A, et al. Cell intrinsic role of COX-2 in pancreatic cancer development. Mol Cancer Ther. 2012;11(10):2127–37.PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Sharma SD, Meeran SM, Katiyar SK. Proanthocyanidins inhibit in vitro and in vivo growth of human non-small cell lung cancer cells by inhibiting the prostaglandin E(2) and prostaglandin E(2) receptors. Mol Cancer Ther. 2010;9(3):569–80.CrossRefPubMedGoogle Scholar
  19. 19.
    Matsubayashi H, Infante JR, Winter J, Klein AP, Schulick R, Hruban R, et al. Tumor COX-2 expression and prognosis of patients with resectable pancreatic cancer. Cancer Biol Ther. 2007;6(10):1569–75.CrossRefPubMedGoogle Scholar
  20. 20.
    Hillion J, Smail SS, Di Cello F, Belton A, Shah SN, Huso T, et al. The HMGA1-COX-2 axis: a key molecular pathway and potential target in pancreatic adenocarcinoma. Pancreatology. 2012;12(4):372–9.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Ding W, DH L. E-calcium adherin and cyclooxygenase-2 expression in cancer of pancreas and its clinical significance. Chin J Gen Surg. 2007;16(05):497–500.Google Scholar
  22. 22.
    Guo MM, Liu JW, Jia FX, Xu YH. Expression of survivin and COX-2 and prognosis of pancreatic cancer patients. Prog Mod Biomed. 2013;13(19):3632–6.Google Scholar
  23. 23.
    Schmid SJ, Glatzel MC, Welke C, Kornmann M, Kleger A, Barth TF, et al. Absence of FLICE-inhibitory protein is a novel independent prognostic marker for very short survival in pancreatic ductal adenocarcinoma. Pancreas. 2013;42(7):1114–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.CrossRefPubMedGoogle Scholar
  25. 25.
    Zintzaras E, Ioannidis JP. HEGESMA: genome search meta-analysis and heterogeneity testing. Bioinformatics. 2005;21(18):3672–3.CrossRefPubMedGoogle Scholar
  26. 26.
    Zintzaras E, Ioannidis JP. Heterogeneity testing in meta-analysis of genome searches. Genet Epidemiol. 2005;28(2):123–37.CrossRefPubMedGoogle Scholar
  27. 27.
    Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of two methods to detect publication bias in meta-analysis. JAMA. 2006;295(6):676–80.CrossRefPubMedGoogle Scholar
  28. 28.
    Gao F, Feng YZ, Deng HZ, Li F. The expression of COX-2 in pancreatic carcinoma and its clinical significance. Suzhou Univ J Med Sci. 2005;25(03):466–8.Google Scholar
  29. 29.
    Juuti A, Louhimo J, Nordling S, Ristimaki A, Haglund C. Cyclooxygenase-2 expression correlates with poor prognosis in pancreatic cancer. J Clin Pathol. 2006;59(4):382–6.PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Ali S, El-Rayes BF, Sarkar FH, Philip PA. Simultaneous targeting of the epidermal growth factor receptor and cyclooxygenase-2 pathways for pancreatic cancer therapy. Mol Cancer Ther. 2005;4(12):1943–51.CrossRefPubMedGoogle Scholar
  31. 31.
    Hermanova M, Trna J, Nenutil R, Dite P, Kala Z. Expression of COX-2 is associated with accumulation of p53 in pancreatic cancer: analysis of COX-2 and p53 expression in premalignant and malignant ductal pancreatic lesions. Eur J Gastroenterol Hepatol. 2008;20(8):732–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Zhao D, Xu D, Zhang X, Wang L, Tan W, Guo Y, et al. Interaction of cyclooxygenase-2 variants and smoking in pancreatic cancer: a possible role of nucleophosmin. Gastroenterology. 2009;136(5):1659–68.CrossRefPubMedGoogle Scholar
  33. 33.
    Yip-Schneider MT, Sweeney CJ, Jung SH, Crowell PL, Marshall MS. Cell cycle effects of nonsteroidal anti-inflammatory drugs and enhanced growth inhibition in combination with gemcitabine in pancreatic carcinoma cells. J Pharmacol Exp Ther. 2001;298(3):976–85.PubMedGoogle Scholar
  34. 34.
    Sanlioglu AD, Dirice E, Elpek O, Korcum AF, Balci MK, Omer A, et al. High levels of endogenous tumor necrosis factor-related apoptosis-inducing ligand expression correlate with increased cell death in human pancreas. Pancreas. 2008;36(4):385–93.CrossRefPubMedGoogle Scholar
  35. 35.
    Hyde CA, Missailidis S. Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis. Int Immunopharmacol. 2009;9(6):701–15.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Di Wang
    • 1
  • Xiao-Zhong Guo
    • 1
  • Hong-Yu Li
    • 1
  • Jia-Jun Zhao
    • 1
  • Xiao-Dong Shao
    • 1
  • Chun-Yan Wu
    • 1
  1. 1.Department of GastroenterologyBeifang Hospital of ShenyangShenyangPeople’s Republic of China

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