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研究生:黃浩雲
研究生(外文):Hao-Yun Huang
論文名稱:在頭頸部鱗狀上皮癌中 T 和 Tn 抗原表現與癌病相關性
論文名稱(外文):Expression of T and Tn antigen in head and neck squamous cell carcinoma
指導教授:黃敏銓黃敏銓引用關係
指導教授(外文):Min-Chuan Huang
口試委員:黃約翰張修豪陳啟豪何宛玲
口試日期:2014-07-30
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:解剖學暨細胞生物學研究所
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:2014
畢業學年度:102
語文別:中文
論文頁數:51
中文關鍵詞:O 型醣化修飾頭頸部鱗狀上皮癌Tn 抗原T 抗原
外文關鍵詞:O-glycansSquamous cell carcinoma of head and neckTn antigenT antigen
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細胞中蛋白質主要的兩種醣化修飾是N-linked glycoproteins 及 O-linked glycoprotein。Tn 抗原和T 抗原是O型糖化中修飾的前兩個醣基團。在許多癌症病人組織中,醣類抗原的表現會出現異常,導致組織中Tn 抗原和T 抗原的大量表現,發生的原因至今仍不明確。本次實驗取台大醫院的175個病人檢體,以凝集素針對Tn 抗原與T 抗原進行免疫組織染色,觀察在頭頸部鱗狀上皮癌切片中Tn 抗原與T 抗原的表現強度。以VVA偵測Tn表現量,結果顯示,相較於非腫瘤組織,71%的腫瘤組織,有較高的Tn 抗原表現量;以PNA偵測T表現量,結果顯示,相較於非腫瘤組織,69%的腫瘤組織,有較高的T 抗原表現量。之後統計抗原表現強度與各種病理診斷因子的臨床相關性。結果顯示,T 抗原在組織中表現量與淋巴血管浸潤(lymphovascular invasion,LVI)、淋巴結被膜外擴散(Extracapsular spread,ECS)、N stage及癌症分期(clinical stage)呈顯著相關(P<0.05)。腫瘤學上認為LVI、ECS、N stage是發生淋巴及遠端轉移的重要指標。目前對於上皮癌中T 抗原的表現在病理學上的影響仍不明確,未來仍需更多研究闡明T抗原的表現在頭頸部鱗狀上皮癌中對於轉移和癌症進程所扮演的角色。

N-linked glycoproteins and O-linked glycoproteins are two main glycoproteins in human cells. Tn and T antigens are the first two glycan units on O-linked glycan chain. Aberrant glycosylation is commonly found in tumors. Many studies have reported an increased Tn and T antigen expression is associated with tumor cell malignancy. However, the underlying mechanism resulting in altered Tn and T antigen expression in tumor malignancies are still poorly understood. In this study, we investigated the expression of the Tn and T antigens in 175 head and neck squamous cell carcinoma patients by immunohistochemistry staining with Vicia villosa agglutinin (VVA) lectin, specific for Tn antigen; and peanut agglutinin (PNA) lectin, specific for T antigen recognition. Our results indicate 71% of the patients display higher Tn antigen expression levels in the tumors compared with the corresponding non-tumor tissues; and 69% of the patients exhibit higher T antigen expression levels in the tumors compared with the corresponding non-tumor tissues. Furthermore, we examined whether Tn and T antigen expression levels correlate with HNSCC clinical pathophysiology. Patients identified with low T antigen expression levels were associated with lymphovascular invasion (LVI), extracapsular spread (ECS), and advanced N stage (P<0.05). LVI, ECS, and N stage are associated with metastasis to lymph nodes or distant sites and high risk of clinical progression. Currently, the implication of aberrant glycosylation and altered Tn and T antigen expressions in cancer malignancies remain unclear. Further studies on the regulation and functional significance of Tn and T antigen occurrence are still required in the understanding of HNSCC progression and metastasis.

目 錄
誌謝…………………………………………………………………………………………1
中文摘要……………………………………………………………………………2
英文摘要………………………………………………………………………………3
一、前言………………………………………………………………………………5
1.1 研究動機………………………………………………………………6
1.2 頭頸部鱗狀上皮細胞癌……………………………………………………6
1.3 蛋白質醣化……………………………………………………7
1.4 N-glycosylation………………………………………………………7
1.5 O-glycosylation……………………………………………………8
1.6 癌症與醣化的關係……………………………………………………8
1.7 Tn抗原和T抗原……………………………………………………9
1.8 Tn 抗原……………………………………………………………9
1.9 T 抗原……………………………………………………………9
1.10 O型醣化修飾的步驟……………………………………………………10
1.11凝集素PNA、VVA……………………………………………………10
二、實驗與材料……………………………………………………………………………11
2. 1檢體………………………………………………………………………12
2.2 切片…………………………………………………………………………12
2.3 免疫染色…………………………………………………………………12
2.4 分數統計與資料分析………………………………………………………13
2.5 資料統計分析……………………………………………………………13
2.6 抗原表現位置………………………………………………………………14
三、結果……………………………………………………………………………… 15
3.1 以凝集素VVA進行免疫組織染色,偵測病人成對檢體中Tn抗原的表現量…………………………………………………………………………………16
3.2 以凝集素VVA進行免疫組織染色,偵測病人非腫瘤與腫瘤檢體中Tn抗原的表現量…………………………………………………………………………………16
3.3 以凝集素PNA進行免疫組織染色,偵測病人成對檢體中T抗原的表現量…………………………………………………………………………………16
3.4 以凝集素PNA進行免疫組織染色,偵測病人非腫瘤與腫瘤檢體中T抗原的表現量……………………………………………………………………………………17
3.5 以凝集素VVA進行免疫組織染色,偵測病人Tn抗原在腫瘤檢體中的表現情形………………………………………………………………………………………17
3.6 以凝集素PNA進行免疫組織染色,偵測病人T抗原在腫瘤檢體中的表現情形…………………………………………………………………………………………17
3.7 以凝集素VVA做免疫染色,偵測癌細胞中Tn抗原在胞內的分布情況……………………………………………………………………………………18
3.8 以凝集素PNA做免疫染色,偵測癌細胞中T抗原在胞內的分布情況…………………………………………………………………………………18
3.9 VVA及PNA染色區域病理型態…………………………………………18
3.10 Tn antigen表現量和臨床資料的相關性………………………………19
3.11 T antigen表現量和臨床資料的相關性……………………………………19
3.12 術後病人存活統計……………………………………………………………19
3.13 Tn antigen與病人術後存活率…………………………………………20
3.14 T antigen與病人術後存活率……………………………………………20
四、討論……………………………………………………………………………………… 21
4.1 Tn 抗原的細胞表現位置……………………………………………………22
4.2 T抗原的細胞表現位置……………………………………………………22
4.3 T抗原表現的組織特異性……………………………………………………23
4.4 T 抗原與臨床因子的相關性………………………………………………23
4.5術後存活率………………………………………………………………………24
4.6 總結…………………………………………………………………………………25
4.7未來研究:O型糖化修飾蛋白所扮演的角色……………………………………25
五、參考文獻………………………………………………………………………………… 26
六、實驗結果與圖表………………………………………………………………………………31
圖一、O型醣化修飾的步驟…………………………………………………………32
圖二、以凝集素VVA進行免疫組織染色,偵測病人成對檢體中Tn抗原的表現量……………………………………………………………………………………………34
圖三、以凝集素VVA進行免疫組織染色,偵測病人非腫瘤與腫瘤檢體中Tn抗原的表現量……………………………………………………………………………………35
圖四、以凝集素PNA進行免疫組織染色,偵測病人成對檢體中T抗原的表現量…………………………………………………………………………………………37
圖五、以凝集素PNA進行免疫組織染色,偵測病人非腫瘤與腫瘤檢體中T抗原的表現量………………………………………………………………………………………38
圖六、以凝集素VVA進行免疫組織染色,偵測病人Tn抗原在腫瘤檢體中的表現情形………………………………………………………………………………………40
圖七、以凝集素PNA進行免疫組織染色,偵測病人T抗原在腫瘤檢體中的表現情形……………………………………………………………………………………41
圖八、以凝集素VVA做免疫染色,偵測癌細胞中Tn抗原在胞內的分布情況……………………………………………………………………………………………42
圖九、以凝集素PNA做免疫染色,偵測癌細胞中T抗原在胞內的分布情況
……………………………………………………………………………………………43
圖十、VVA及PNA染色區域病理型態…………………………………………………44
圖十一、Tn antigen表現量和臨床資料的相關性……………………………45
圖十二、T antigen表現量和臨床資料的相關性……………………………46
圖十三、Tn antigen與病人術後存活率…………………………………47
圖十四、T antigen與病人術後存活率……………………………………48
圖十五、T antigen表現量對分化程度高低之相關性…………………………49
表一、使用於免疫組織染色的凝集素濃度與呈色時間…………………………50
表二、術後病人存活統計………………………………………………………51


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