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研究生:鞠沅東
研究生(外文):Yuan-Tung Chu
論文名稱:探討有絲分裂標記Anti-phospho-Histone H3在大腸直腸癌的表現與預後因子的相關性
論文名稱(外文):Expression of Mitosis Marker Anti-phospho-Histone H3 in Human Colorectal Cancer and correlation with classic Prognostic Factor
指導教授:王淑慧王淑慧引用關係
口試委員:龔秀妮陳金銓王仰高
口試日期:2015-07-03
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:2015
畢業學年度:103
語文別:中文
論文頁數:32
中文關鍵詞:磷酸化組織蛋白H3大腸直腸癌p53Ki-67
外文關鍵詞:phospho-Histone H3colorectal cancerp53ki-67
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大腸直腸癌是在世界上最主要的惡性腫瘤死亡原因而且病因牽涉多重複雜的步驟和因子。因此,鑑別有用的預後標記將有利於發展對大腸直腸癌合理的治療策略。磷酸化組織蛋白H3(phospho-Histone H3, PHH3)是一個新的定量有絲分裂的免疫組織化學染色標記。然而,PHH3有關大腸直腸癌預後的訊息很十分有限。本實驗的主要目的探索PHH3在大腸直腸癌預後扮演的角色,探討新細胞分化標記PHH3和已確立的細胞分化標記Ki-67和腫瘤抑制蛋白p53標記之間的相關性和判斷它們與大腸直腸癌預後的關聯性。
在本實驗有164病例根據蘇木紫-伊紅染色(Hematoxylin & Eosin stain) 和PHH3、 Ki-67和p53的免疫組織化學染色方法分析臨床病理參數。根據研究結果顯示,與鄰近正常大腸黏膜相比PHH3在腫瘤表現有顯著的增加。PHH3的表現與大腸直腸癌分化(P<0.05)、臨床分期(P<0.05)、神經侵犯(P<0.001)、M分期(P<0.05)有顯著意義。
在存活分析中,與低PHH3表現的病例相比,高PHH3表現較長的整體存活和較好的無轉移存活率。依據價值評估,與Ki-67和p53相比PHH3有較高的預後價值,而且有常規實驗診斷的潛在價值。
PHH3的表現與大腸直腸癌的發生和進展有顯著的相關性。或許PHH3可能建立一個預防大腸直腸癌有用的分子標的或引導改善治療大腸直腸癌的治療方法。PHH3可能是一個有用的預測大腸直腸癌疾病結果的預測因子。


Colorectal cancer (CRC) has a complex pathogenesis involving multiple steps and factors, and is one of the most common causes of cancer deaths worldwide. Thus, the identification of useful prognostic markers that exert a strong prognostic impact for CRC progression would be beneficial in the development of rational therapeutic strategies. Phosphohistone H3 (PHH3) is a new marker for quantifying mitoses; however, there is limited information on the prognostic value of PHH3 in patients with CRC. The aim of the current study was to determine the role of PHH3 as a prognostic factor in patients with CRC and to elucidate the relationships between the novel proliferation marker, PHH3, the established cell proliferating marker, Ki-67, and the tumor suppressor, p53, and the prognostic relevance in patients CRC.
One hundred sixty-four CRC patients were included in the current study. Clinicopathologic parameters were analyzed by H&E staining and immunohistochemical staining for PHH3, Ki-67, and p53. The expression of PHH3 was significantly increased in CRC tissues compared to adjacent normal colorectal mucosal tissues. PHH3 expression was significantly associated with CRC differentiation (P<0.05), clinical staging (P<0.05), perineural invasion (P<0.001), and metastasis (p< 0.05). Patients with high PHH3 expression had longer overall survival and better metastasis-free survival rates than patients with low PHH3 expression. PHH3 had a greater prognostic value than Ki-67 and p53 in CRC patients, and thus potential for use in routine diagnostic laboratories.
The expression of PHH3 is highly related to CRC detection and significantly correlated to the progression of CRC. PHH3 may constitute a useful molecular target for CRC prevention or may led to improved therapeutic modalities for this common cancer. PHH3 may be a useful prognostic factor for the prediction of disease outcome in patients with CRC.


致謝.......................................................Ⅱ
摘要.......................................................Ⅲ
Abstract...................................................IV
Table of contents...........................................V
第一章 緒論................................................1
1.1大腸直腸.................................................1
1.2大腸直腸癌發生的病因.....................................1
1.3大腸直腸癌的血液腫瘤標記.................................3
1.4大腸直腸癌分期和預後.....................................3
1.5 Ki-67細胞增殖標記.......................................5
1.6磷酸化組織蛋白H3.........................................5
1.7 磷酸化組織蛋白H3的臨床應用..............................6
第二章 研究目的............................................9
第三章 研究方法與材料.....................................10
3.1 病人收錄與排除條件.....................................10
3.2 蘇木紫-伊紅染色........................................10
3.3 免疫組織化學染色.......................................10
3.4 PHH3有絲分裂數目的計算.....................................11
3.5 Ki-67與P53的免疫染色結果計算方法......................11
3.6 西方墨點法.............................................11
3.7 統計方法...............................................11
第四章 結果...............................................12
第五章 討論...............................................15
第六章 結論...............................................17
圖1-1 (緒論)................................................1
圖1-2 (緒論)................................................2
圖1-3 (緒論)................................................5
圖1-4 (緒論)................................................8
圖4-1......................................................18
圖4-2......................................................18
表4-1......................................................19
表4-2......................................................21
表4-3......................................................21
圖4-3......................................................22
圖4-4......................................................23
表4-4......................................................24
表4-5......................................................26
參考文獻...................................................28



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