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研究生:陳志榮
研究生(外文):Chih-Jung Chen
論文名稱:IL6及IL10在口腔癌之臨床預後角色之研究
論文名稱(外文):The Role of IL6 and IL10 in Clinical Prognosis in Oral Cancer
指導教授:葉坤土葉坤土引用關係柯俊良柯俊良引用關係
學位類別:博士
校院名稱:中山醫學大學
系所名稱:醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:99
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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。

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.

第一章 中文摘要 1
第二章 英文摘要 3
第三章 縮寫表 (Abbreviations) 5
第四章 緒論 6
一、口腔癌的重要性的背景概述 6
二、吸菸、喝酒和口腔癌的相關性的概述 8
三、嚼檳榔和口腔癌的相關性的概述 9
四、人類乳突病毒 (human papillomavirus, HPV) 和人類癌症的相關性的概述 10
五、 人類乳突病毒 (human papillomavirus, HPV) 和口腔癌的相關性的概述 14
六、 女性口腔癌的概述 16
七、 Interleukin 6 (IL6) 在癌症的發生和疾病進展的角色 18
八、 Interleukin 6 (IL6) 與口腔癌 20
九、 Interleukin 10 (IL10) 在癌症的發生和疾病進展的角色 21
十、 Interleukin 10 (IL10) 和口腔癌 23
第五章 研究動機 25
第六章 實驗設計 26
一、 使用組織微矩陣 (tissue microarrays; TMAs)來做大規模口腔癌組織的組織學及免疫組織化學染色的觀察 26
二、 使用免疫組織化學 (IHC) 染色分析IL6蛋白的表現 26
三、 使用免疫組織化學 (IHC) 染色分析IL10蛋白的表現 27
四、 使用免疫組織化學 (IHC) 染色分析HPV16 E6蛋白的表現 27
五、 使用統計方法分析口腔癌病人的臨床病理特徵和IL6蛋白、IL10蛋白及HPV16 E6蛋白的相關性 27
第七章 研究材料與研究方法 28
一、 患者收集 28
二、 實驗材料 29
三、 實驗儀器 30
四、 組織微陣列晶片 (tissue microarrays; TMAs) 的製作 31
五、 免疫組織化學 (IHC) 染色分析IL6、IL10和HPV16 E6 的表現 33
(一) 免疫組織化學 (IHC) 染色分析IL6的表現 34
(二) 免疫組織化學 (IHC) 染色分析IL10的表現 35
(三) 免疫組織化學 (IHC) 染色分析HPV16 E6蛋白的表現 ………………………………………………………….36
六、 統計分析 36
第八章 結果 38
一、 IL6病患的基本特性 38
二、 IL6 在口腔癌腫瘤組織或分化不良性口腔上皮細胞的表現高於相鄰正常組織 39
三、 腫瘤細胞IL6的表現量和臨床病理特徵之間的相關性 40
四、 以腫瘤細胞之IL6 表達量來看在口腔癌病人的臨床預後價值 41
五、 IL10病患的基本特性 44
六、 IL10在口腔癌腫瘤組織或分化不良性口腔上皮細胞的表現高於相鄰正常組織 45
七、 腫瘤細胞IL10的表現量和臨床病理特徵之間的相關性 46
八、 以腫瘤細胞之 IL10表達量來看在口腔癌病人的臨床預後價值 46
第九章 討論 50
第十章 參考文獻 64
第十一章 圖表 79
第十二章 論文抽印本 99


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