IL6及IL10在口腔癌之臨床預後角色之研究

口腔鱗狀細胞癌 (oral squamous cell carcinoma; OSCC) 是一種以男性為主，而且臨床預後很差的惡性腫瘤。由於女性病例相對較少，所以，之前很少研究著重於討論在不同性別的口腔癌間是否存在影響預後的標誌物。Interleukin 6 (IL6) 是一種具有抗發炎的人類介白素，在人類癌症發生過程中，扮演重要的角色。Interleukin 10 (IL10) 是另一種人類介白素，在免疫抑制與抑制抗腫瘤免疫反應中，有著重要的影響。本研究利用組織微陣列與免疫組織化學染色方法，來分析口腔癌患者的組織檢體。我們發現腫瘤細胞中IL6的高表現，與口腔癌患者有相關的因子如下：女性、較高的淋巴結轉移率和較差的腫瘤分化。腫瘤中IL6的表現高，在男性患者的總存活期較短，在女性則無此現象。回歸分析也顯示，在男性口腔癌患者中，腫瘤細胞中IL6的高表現與預後差有關，其死亡風險為1.493倍。所以，腫瘤細胞的IL6表現高，與患者具有較差的臨床表現有顯著相關，特別是在男性口腔癌病人，IL6可能是一個獨立的存活預測因子。另外我們發現腫瘤細胞IL10的高表現和口腔癌患者有相關的因子包含：男性、吸菸、喝酒、嚼檳榔、較短的無復發狀況之存活期、和較短的總存活期。IL10表現高的腫瘤，特別是早期癌症的患者，其總存活期較短。在回歸分析顯示，在早期的口腔癌患者，腫瘤IL10表現高，其死亡風險較高，為1.990倍。所以，IL10表現高的腫瘤，患者具有較差的臨床表現，尤其是在早期口腔癌患者中，可能是一個獨立的存活預測因子。另外，我們發現IL6或IL10在口腔癌細胞的表現量及與臨床預後的相關性，和人類乳突病毒第16型E6蛋白的表現與否，並沒有相關。

關鍵字

口腔癌；介白素六；介白素十；預後

並列摘要

Oral squamous cell carcinoma (OSCC) is a malignant tumor of the oral cavity with a male predominant tendency and a poor clinical prognosis. Due to the relatively few cases in females, the gender difference of prognostic markers for OSCC is seldom discussed. Interleukin 6 (IL6), a kind of human interleukins, plays an important role in anti-inflammation and tumorigenesis in human cancers. Interleukin 10 (IL10), another kind of human interleukins, plays an important role in immunosuppression and suppression of antitumor immunity. In this study, we used tissue microarray and immunohistochemical staining methods to investigate the patients’ cancer specimens. We found that high IL6 expression in tumor cells was significantly associated OSCC patient characteristics including female gender, high lymph node metastatic rate, and poor tumor differentiation. Tumor-expressed IL6 had prognostic role in male OSCC patients, but not in female patients. In male OSCC patients, high IL6 expression in tumor cells was associated with poor prognosis and a 1.493-fold higher death risk, as determined by Cox regression. We had a conclusion that high IL6 expression in tumor cells was therefore significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in male OSCC patients. We found that high IL10 expression in OSCC patients was significantly associated with male gender, smoking, alcohol consumption, betel quid chewing, poor relapse free survival, and poor overall survival. Patients with high IL10 expression, and particularly early stage OSCC patients, had significantly worse overall survival. In early stage patients, high IL10 expression in tumor cells was associated with poor prognosis and a 1.990-fold higher death risk, as determined by Cox regression. We had a conclusion that high IL10 expression is significantly associated with aggressive clinical manifestations and might be an independent survival predictor, particularly in early stage OSCC patients. In addition, there was no association with human papillomavirus (HPV) 16 E6 protein and IL6 or IL10 expression as well as their impacts in clinical prognosis.

並列關鍵字

oral cancer ； interleukin 6 ； interleukin 10 ； prognosis

參考文獻

Gaiolla, R.D., Domingues, M.A., Niero-Melo, L., and de Oliveira, D.E. (2011). Serum levels of interleukins 6, 10, and 13 before and after treatment of classic Hodgkin lymphoma. Arch. Pathol. Lab. Med. 135, 483-489.

Aggarwal, B.B., Shishodia, S., Sandur, S.K., Pandey, M.K., and Sethi, G. (2006). Inflammation and cancer: how hot is the link? Biochem. Pharmacol. 72, 1605-1621.

Alhamarneh, O., Agada, F., Madden, L., Stafford, N., and Greenman, J. (2011). Serum IL10 and circulating CD4(+) CD25(high) regulatory T cell numbers as predictors of clinical outcome and survival in patients with head and neck squamous cell carcinoma. Head Neck 33, 415-423.

Ang, K.K., Harris, J., Wheeler, R., Weber, R., Rosenthal, D.I., Nguyen-Tan, P.F., Westra, W.H., Chung, C.H., Jordan, R.C., Lu, C., et al. (2010). Human papillomavirus and survival of patients with oropharyngeal cancer. N. Engl. J. Med. 363, 24-35.

Argiris, A., Karamouzis, M.V., Raben, D., and Ferris, R.L. (2008). Head and neck cancer. Lancet 371, 1695-1709.

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IL6及IL10在口腔癌之臨床預後角色之研究

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