IL-10表現性於陽性及陰性HPV-16口腔鱗狀細胞癌間存活與復發之不同影響

背景人類乳突病毒（human papilloma virus，HPV）是口咽癌已知的危險因子之一；然而HPV在台灣口腔鱗狀細胞癌（oral squamous cell carcinoma，OSCCs）患者中所扮演的角色尚未完全釐清。本研究在探討介白素10（interleukin-10，IL-10）的表現性對陽性HPV與陰性HPV口腔鱗狀細胞癌兩者間的整體存活（overall survival，OS）和無復發存活（relapse free survival，RFS）是否有不同的影響。材料與方法本研究收集自2001年至 2010年口腔鱗狀細胞癌患者的口腔腫瘤檢體石蠟切片共178例，其中吸菸、喝酒及嚼食檳榔等危險因子都沒有的患者有61例，有一個或一個以上前述三危險因子的患者有117例，用以驗證HPV16/18感染是否為無吸菸，無喝酒及無嚼食檳榔之口腔鱗狀細胞癌患者的危險因子。HPV16/18 DNA、IL-10 mRNA 及p16蛋白分別以巢式聚合酶鏈鎖反應（nested-PCR）、即時聚合酶鏈鎖反應（real-time PCR）和免疫組織化學方法進行檢測評估。我們用Kaplan-Meier存活分析及Cox回歸模式來分析IL-10 mRNA對口腔鱗狀細胞癌的OS和RFS的影響。結果無吸菸，無喝酒及無嚼食檳榔的口腔鱗狀細胞癌患者其HPV16/18 感染率高於有吸菸、喝酒嚼食檳榔的口腔鱗狀細胞癌患者；也顯示HPV感染的口腔鱗狀細胞癌與IL-10的表現有關。陽性HPV患者比陰性HPV患者有比較高的IL-10 mRNA表現量。高IL-10 mRNA表現量的患者比低IL-10 mRNA表現量的患者有較短的OS和RFS。IL-10 mRNA表現量的高低只可以在陽性HPV的口腔鱗狀細胞癌患者上觀察到對其OS和RFS存活的預後具有顯著差異，但在陰性HPV口腔鱗狀細胞癌患者則無此現象。IL-10在口腔鱗狀細胞癌細胞的表現量會因E6過度表現而增加並且會因E6減少而減少。HPV16/18 E6造成的IL-10表現量升高會使陽性HPV口腔鱗狀細胞癌患者的癌細胞群落形成和轉移能力增加，可能進而導致其預後變差及復發。結論本研究顯示被E6誘發的IL-10會促進陽性HPV口腔鱗狀細胞癌的細胞生長和轉移能力增加，進而導致其預後變差及復發。

關鍵字

介白素-10 ；人類乳突病毒；預後；復發；口腔鱗狀細胞癌

並列摘要

Background Human papillomavirus (HPV) is a risk factor in a subset of oropharyngeal cancer; however, the contribution of HPV in the malignancy of oral squamous cell carcinomas (OSCC) is not fully understood in Taiwanese. Materials and methods Herein, OSCC tumor specimens were collected between 2001 and 2010 from 178 patients with primary oral cancers. 61 patients with no risk factors and 117 patients with one or more risk factors were enrolled in this study. HPV16/18 DNA, interleukin-10 (IL-10) mRNA and p16 protein were determined by nested-PCR, real-time PCR and immunohistochemistry, respectively. The prognostic value of IL-10 mRNA on OS and RFS was evaluated by Kaplain-Meier and Cox-regression models. Results HPV16/18 infection rate in non-smokers, non-drinkers and non-betel quid chewers was higher than their counterparts. The development of HPV-infected cancer has been shown to be associated with IL-10 expression. To this end, IL-10 mRNA expression in OSCC tumors was evaluated by real-time RT-PCR. Data showed that HPV-positive patients had higher IL-10 mRNA levels than in HPV-negative patients. Kaplan-Meier and Cox-regression analysis indicated that the prognostic significance of IL-10 mRNA on overall survival and relapse free survival was only observed in HPV-positive OSCC, but not in HPV-negative OSCC. Mechanistically, the elevation of IL-10 by E6 was responsible for increased colony formation and migration capability in OSCC cells. Conclusions We suggest that IL-10 induced by E6 promotes cell growth, migration capability, consequent poor survival and relapse in HPV-positive OSCC.

並列關鍵字

IL-10 ； HPV ； prognosis ； relapse ； oral squamous cell carcinomas

參考文獻

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IL-10表現性於陽性及陰性HPV-16口腔鱗狀細胞癌間存活與復發之不同影響

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