Cyclooxygenase-2 Expression and Its Correlation with Primary Tumor Size and Lymph Node Involvement in Nasopharyngeal Carcinoma
DOI:
https://doi.org/10.3889/oamjms.2018.356Keywords:
Overexpression, Cyclooxygenase (COX)-2, Nasopharyngeal carcinoma, Tumor Size, Lymph node involvementAbstract
AIM: This study aimed to observe the cyclooxygenase-2 expression and its correlation with tumour size and lymph node involvement in nasopharyngeal carcinoma.
METHODS: This study was cross-sectional, that enrolled 126 samples diagnosed with nasopharyngeal carcinoma in Haji Adam Malik General Hospital, Medan, Indonesia which fulfilled the inclusion criteria.
RESULTS: Based on this study, we found that the age peak incidence of nasopharyngeal carcinoma patients about a 41-60-year-old group (57.1%), dominated by men (71.4%). Through histopathological examination, non-keratinizing squamous cell carcinoma is the most predominant type (79.4%). We also found T3 is the most prevalent primary tumour size (32.5%) with prominent lymph node involvement N3 (45.2%), and stage IV (54.8%). Cyclooxygenase-2 overexpression is prevalent among nonkeratinizing squamous cell carcinoma (81.1%), T3 primary tumour size (41.1%), N3 node involvement (60.0%), and IV clinical stage (71.6%). In addition, we found a significant relationship between cyclooxygenase-2 expressions towards tumor size (p < 0.001) and lymph node involvement (p < 0.001) in nasopharyngeal carcinoma.
CONCLUSION: It is proved that the overexpression of cyclooxygenase-2 will increase the susceptibility of nasopharyngeal carcinoma patients having advanced primary tumour size and lymph node involvement.
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Chua ML, Wee JT, Hui EP, Chan AT. Nasopharyngeal carcinoma. The Lancet. 2016; 387(10022):1012-24. https://doi.org/10.1016/S0140-6736(15)00055-0
Wang Z, Dabrosin C, Yin X, Fuster MM, Arreola A, Rathmell WK, Generali D, Nagaraju GP, El-Rayes B, Ribatti D, Chen YC. Broad targeting of angiogenesis for cancer prevention and therapy. In Seminars in cancer biology. 2015; 35:S224-S243. https://doi.org/10.1016/j.semcancer.2015.01.001 PMid:25600295 PMCid:PMC4737670
Adham M, Kurniawan AN, Muhtadi AI, Roezin A, Hermani B, Gondhowiardjo S, Tan IB, Middeldorp JM. Nasopharyngeal carcinoma in Indonesia: epidemiology, incidence, signs, and symptoms at presentation. Chinese journal of cancer. 2012; 31(4):185. https://doi.org/10.5732/cjc.011.10328 PMid:22313595 PMCid:PMC3777476
Divvela AK, Challa SR, Tagaram IK. Pathogenic role of cyclooxygenase-2 in cancer. Journal of Health Science. 2010; 56(5):502-16. https://doi.org/10.1248/jhs.56.502
Smith WL, Song I. The enzymology of prostaglandin endoperoxide H synthases-1 and-2. Prostaglandins & other lipid mediators. 2002; 68:115-28. https://doi.org/10.1016/S0090-6980(02)00025-4
Chen W, Hu GH. Biomarkers for enhancing the radiosensitivity of nasopharyngeal carcinoma. Cancer biology & medicine. 2015; 12(1):23. PMid:25859408 PMCid:PMC4383846
Sobolewski C, Cerella C, Dicato M, Ghibelli L, Diederich M. The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. International journal of cell biology. 2010; 2010.
Liu B, Qu L, Yan S. Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer cell international. 2015; 15(1):106. https://doi.org/10.1186/s12935-015-0260-7 PMid:26549987 PMCid:PMC4635545
Dixon DA. Regulation of COX-2 expression in human cancers. COX-2. 2003; 37:52-71).
Rouzer CA, Marnett LJ. Cyclooxygenases: structural and functional insights. Journal of lipid research. 2009; 50(Suppl):S29-34. https://doi.org/10.1194/jlr.R800042-JLR200 PMid:18952571 PMCid:PMC2674713
Clà ria J. Cyclooxygenase-2 biology. Current pharmaceutical design. 2003; 9(27):2177-90. https://doi.org/10.2174/1381612033454054 PMid:14529398
Gately S, Li WW. Multiple roles of COX-2 in tumor angiogenesis: a target for antiangiogenic therapy. Seminars in Oncology. 2004; 31:2-11. https://doi.org/10.1053/j.seminoncol.2004.03.040 PMid:15179620
Imig JD. Epoxyeicosatrienoic acids and 20-hydroxyeicosatetraenoic acid on endothelial and vascular function. Advances in Pharmacology. 2016; 77:105-141. https://doi.org/10.1016/bs.apha.2016.04.003 PMid:27451096 PMCid:PMC5510644
Liu CH, Chang SH, Narko K, Trifan OC, Wu MT, Smith E, Haudenschild C, Lane TF, Hla T. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. Journal of Biological Chemistry. 2001; 276(21):18563-9. https://doi.org/10.1074/jbc.M010787200 PMid:11278747
Huang T, Chen MH, Wu MY, Wu XY. Correlation between expression of extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 and cervical lymph node metastasis of nasopharyngeal carcinoma. Annals of Otology, Rhinology & Laryngology. 2013; 122(3):210-5. https://doi.org/10.1177/000348941312200311 PMid:23577575
Lasek W, Zagożdżon R, Jakobisiak M. Interleukin 12: still a promising candidate for tumor immunotherapy? Cancer Immunology, Immunotherapy. 2014; 63(5):419-435. https://doi.org/10.1007/s00262-014-1523-1 PMid:24514955 PMCid:PMC3994286
Gately S. The contributions of cyclooxygenase-2 to tumor angiogenesis. Cancer and metastasis reviews. 2000; 19(1-2):19-27. https://doi.org/10.1023/A:1026575610124 PMid:11191059
Iwata C, Kano MR, Komuro A, Oka M, Kiyono K, Johansson E, Morishita Y, Yashiro M, Hirakawa K, Kaminishi M, Miyazono K. Inhibition of cyclooxygenase-2 suppresses lymph node metastasis via reduction of lymphangiogenesis. Cancer Research. 2007; 67(21):10181-9. https://doi.org/10.1158/0008-5472.CAN-07-2366 PMid:17974958
Lu X, Qian CN, Mu YG, Li NW, Li S, Zhang HB, Li SW, Wang FL, Guo X, Xiang YQ. Serum CCL2 and serum TNF-α–Two new biomarkers predict bone invasion, post-treatment distant metastasis and poor overall survival in nasopharyngeal carcinoma. European journal of cancer. 2011; 47(3):339-46. https://doi.org/10.1016/j.ejca.2010.09.025 PMid:20951575
Elliott LA, Doherty GA, Sheahan K, Ryan EJ. Human tumor-infiltrating myeloid cells: phenotypic and functional diversity. Frontiers in immunology. 2017; 8:86. https://doi.org/10.3389/fimmu.2017.00086 PMid:28220123 PMCid:PMC5292650
Schmid MC, Varner JA. Myeloid cells in the tumor microenvironment: modulation of tumor angiogenesis and tumor inflammation. Journal of oncology. 2010; 2010.
Cotechini T, Medler TR, Coussens LM. Myeloid cells as targets for therapy in solid tumors. Cancer journal (Sudbury, Mass.). 2015; 21(4):343. https://doi.org/10.1097/PPO.0000000000000132 PMid:26222088 PMCid:PMC4948591
Iacovelli N, et al. Emerging prognostic factors in Nasopharyngeal carcinoma. Journal of Naso Pharyngeal Carcinoma. 2014; 1(8).
Kim TJ, Lee YS, Kang JH, Kim YS, Kang CS. Prognostic significance of expression of vegf and coxâ€2 in nasopharyngeal carcinoma and its association with expression of Câ€erbB2 and EGFR. Journal of surgical oncology. 2011; 103(1):46-52. https://doi.org/10.1002/jso.21767 PMid:21031415
Chou J, Lin YC, Kim J, You L, Xu Z, He B, Jablons DM. Nasopharyngeal carcinoma—review of the molecular mechanisms of tumorigenesis. Head & Neck: Journal for the Sciences and Specialties of the Head and Neck. 2008; 30(7):946-63. https://doi.org/10.1002/hed.20833 PMid:18446839 PMCid:PMC3046044
Wu YD, Zhou BP. TNF-α/NF-κB/Snail pathway in cancer cell migration and invasion. British journal of cancer. 2010; 102(4):639. https://doi.org/10.1038/sj.bjc.6605530 PMid:20087353 PMCid:PMC2837572
Yang G, Deng Q, Fan W, Zhang Z, Xu P, Tang S, Wang P, Yu M. Cyclooxygenase-2 expression is positively associated with lymph node metastasis in nasopharyngeal carcinoma. PloS one. 2017; 12(3):e0173641. https://doi.org/10.1371/journal.pone.0173641 PMid:28301518 PMCid:PMC5354404
Soo R, Putti T, Tao Q, Goh BC, Lee KH, Kwok-Seng L, Tan L, Hsieh WS. Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and association with epidermal growth factor receptor expression. Archives of Otolaryngology–Head & Neck Surgery. 2005; 131(2):147-52. https://doi.org/10.1001/archotol.131.2.147 PMid:15723947
Fendri A, Khabir A, Hadhri-Guiga B, Sellami-Boudawara T, Ghorbel A, Daoud J, Frikha M, Jlidi R, Gargouri A, Mokdad-Gargouri R. Overexpression of COX-2 and LMP1 are correlated with lymph node in Tunisian NPC patients. Oral oncology. 2008; 44(7):710-5. https://doi.org/10.1016/j.oraloncology.2007.09.006 PMid:18061524
Li WW, Long GX, Liu DB, Mei Q, Wang JF, Hu GY, Jiang JZ, Sun W, Gan L, Hu GQ. Cyclooxygenase-2 inhibitor celecoxib suppresses invasion and migration of nasopharyngeal carcinoma cell lines through a decrease in matrix metalloproteinase-2 and-9 activity. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 2014; 69(2):132-7.
Tan KB, Putti TC. Cyclooxygenase 2 expression in nasopharyngeal carcinoma: immunohistochemical findings and potential implications. Journal of clinical pathology. 2005; 58(5):535-8. https://doi.org/10.1136/jcp.2004.021923 PMid:15858127 PMCid:PMC1770665
Kwong DL, Nicholls J, Sham J. Cyclooxygenase-2 expression in nasopharyngeal carcinoma. International Journal of Radiation. 2007.
Pan J, Tang T, Xu L, Lu JJ, Lin S, Qiu S, Chen G, Tham IW. Prognostic significance of expression of cyclooxygenaseâ€2, vascular endothelial growth factor, and epidermal growth factor receptor in nasopharyngeal carcinoma. Head & neck. 2013; 35(9):1238-47. https://doi.org/10.1002/hed.23116 PMid:22972415
Chen WC, McBride WH, Chen SM, Lee KF, Hwang TZ, Jung SM, Shau H, Liao SK, Hong JH, Chen MF. Prediction of poor survival by cyclooxygenaseâ€2 in patients with T4 nasopharyngeal cancer treated by radiation therapy: Clinical and in vitro studies. Head & Neck: Journal for the Sciences and Specialties of the Head and Neck. 2005; 27(6):503-12. https://doi.org/10.1002/hed.20178 PMid:15772955
Xinhua XU, Guoqing HU, Song LI, Feng XU, Daojun LI, Delan DA, Yan CH. Expression of cyclooxygenase-2 in nasopharyngeal carcinoma and its relation to angiogenesis and prognosis. The Chinese-German Journal of Clinical Oncology. 2006; 5(2):104-7. https://doi.org/10.1007/s10330-005-0400-y
Chang BW, Kim DH, Kowalski DP, Burleson JA, Son YH, Wilson LD, Haffty BG. Prognostic significance of cyclooxygenase-2 in oropharyngeal squamous cell carcinoma. Clinical cancer research. 2004; 10(5):1678-84. https://doi.org/10.1158/1078-0432.CCR-03-0354 PMid:15014019
Gallo O, Masini E, Bianchi B, Bruschini L, Paglierani M, Franchi A. Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma. Human pathology. 2002; 33(7):708-14. https://doi.org/10.1053/hupa.2002.125376 PMid:12196922
Loong SL, Hwang JS, Li HH, Wee JT, Yap SP, Chua ML, Fong KW, Tan TW. Weak expression of cyclooxygenase-2 is associated with poorer outcome in endemic nasopharyngeal carcinoma: analysis of data from randomized trial between radiation alone versus concurrent chemo-radiation (SQNP-01). Radiation Oncology. 2009; 4(1):23. https://doi.org/10.1186/1748-717X-4-23 PMid:19591688 PMCid:PMC2715417
Kim YJ, Lee SH, Wu HG, Go H, Jeon YK. Immunohistochemical study to evaluate the prognostic significance of four biomolecular markers in radiotherapy of nasopharyngeal carcinoma. J Korean Soc Ther Radiol Oncol. 2010; 28(2):57-63. https://doi.org/10.3857/jkstro.2010.28.2.57
Sackett MK, Bairati I, Meyer F, Jobin É, Lussier S, Fortin A, Gélinas M, Nabid A, Brochet F, Têtu B. Prognostic significance of cyclooxygenase-2 overexpression in glottic cancer. Clinical Cancer Research. 2008; 14(1):67-73. https://doi.org/10.1158/1078-0432.CCR-07-2028 PMid:18172254
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