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Author:徐玉珍
Author (Eng.):Yu-Chen Hsu
Title:脯氨酸導引蛋白質激酶FA是個共通的訊號傳遞分子預測癌症惡化和病人存活
Title (Eng.):Proline-Directed Protein Kinase FA (PDPK FA) is a Common Novel Signal Transducing Molecule for Prediction of Cancer Progression and Patient Survival
Advisor:楊孝德
advisor (eng):Shiaw-Der Yang
degree:Ph.D
Institution:國立清華大學
Department:生命科學系
Narrow Field:生命科學學門
Detailed Field:生物學類
Types of papers:Academic thesis/ dissertation
Publication Year:2006
Graduated Academic Year:94
language:English
number of pages:126
keyword (chi):脯氨酸導引蛋白質激酶FA癌症惡化病人存活
keyword (eng):PDPK FACancer ProgressionPatient Survival
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目的:分子、細胞及動物的實驗已證實過度表現的脯氨酸導引蛋白質激酶FA (PDPK FA)對於人類癌細胞的腫瘤形成、侵犯、轉移等被認為是最有潛力且最致命的因子之一,然而,PDPK FA 在實際癌症病人的癒後角色上所知甚少仍待建立,本研究因此完整地系統性探討PDPK FA和致命癌症病人癒後的相關性。
病人和方法:利用免疫組織染色法分別分析134位肝癌病人、150位膽道癌病人和146位胃癌病人外科切除的腫瘤切片中PDPK FA的表現情形。腫瘤細胞質和細胞核具PDPK FA高度濃染者是PDPK FA陽性表現的主要評值依據。所得資料主要是利用醫學統計進行存活分析。
結果:PDPK FA陽性表現的比率在肝癌是68% (91/134)、膽道癌67%(100/150)、胃癌則是58% (84/146),這些PDPK FA陽性表現的病人很明顯地呈現較差的癒後—較易復發、轉移和死亡。克氏多變項比例風險模式進一步建立PDPK FA在肝癌、膽道癌和胃癌的疾病惡化和病人存活上都是最強的獨立癒後預測指標(肝癌復發風險比為2.88、死亡風險比為5.04,膽道癌死亡風險比為3.39,胃癌復發風險比為6.84、死亡風險比為5.36)。PDPK FA若同時合併傳統已建立的癒後變項做存活分析,既使陰性的傳統癒後變項理應癒後良好,但若PDPK FA過度表現實際癒後則非常差,PDPK FA能夠解決早期病人的癒後不確定感。
結論:本研究建立PDPK FA在原發性肝癌、膽道癌和胃癌經外科切除後癒後的重要性,此結果和過去研究發現PDPK FA在促進癌快速惡化的致命性角色一致,PDPK FA是個共通的訊號傳遞分子預測癌症惡化和病人存活。綜言之,PDPK FA在高度侵犯性癌症病人開完刀後癒後的預測與治療上是個全新、可矯正的訊號傳遞標的分子。
Purpose: The molecular, cellular and animal studies have established that overexpressed proline-directed protein kinase FA (PDPK FA) is essential for the development of tumorigenesis, invasion, and metastasis of human cancer cells. However, the prognostic role of PDPK FA in cancer patients remains largely unknown. The present study was comprehensively to examine association of PDPK FA expression with poor prognosis of aggressive cancer patients.
Patients and Methods: PDPK FA expression in the resected tumors of 134 hepatocellular carcinoma (HCC) patients, 150 cholangiocarcinoma (CC) patients, and 146 gastric cancer (GC) patients was analyzed by immunohistochemistry. Highly condensed cytoplasmic and nuclear PDPK FA associated with tumor cells was used as the major scoring parameter for positive PDPK FA expression. Survival analysis was used to analyze the data.
Results: The frequency of positive PDPK FA expression was 68% (91/134) in HCC, 67% (100/150) in CC, and 58% (84/134) in GC, respectively. Patients with positive PDPK FA showed poorer disease-free survival (DFS) and overall survival (OS) (P<0.001 for both). Cox multivariate regression analysis further established PDPK FA as the strongest independent prognosticator for progression and patient survival of HCC (HR 2.878, 95% CI 1.634-5.067 for DFS and HR 5.035, 95% CI 2.137-11.866 for OS, P<0.001), CC (HR 3.386, 95% CI 1.806-6.348 for OS, P<0.001), and GC (HR 6.84, 95% CI 3.43-13.65 for DFS and HR 5.36, 95% CI 2.61-10.98 for OS, P<0.001). Overexpression of PDPK FA was also a particularly unfavorable maker in the combination analysis on the survival data and could resolve the prognostic uncertainties of the early stage patients.
Conclusion: In consistence with its essential role in the development of highly malignant phenotypes, the present study establishes the potential prognostic role of PDPK FA in surgically resected primary HCC, CC and GC. PDPK FA is a common novel molecule for prediction of cancer progression and patient survival. Taken together, PDPK FA represents a new modifiable signal transducing target for prognostic prediction and adjuvant treatment of patients with aggressive cancers after surgical resection.
CONTENTS
CHAPTER 1 Summary 7
CHAPTER 2 General Introduction 8
CHAPTER 3 Patients and Methods 15
CHAPTER 4 Proline-Directed Protein Kinase FA Is A
Novel Independent Prognostic Predictor in
Hepatocellular Carcinoma 22
CHAPTER 5 Proline-Directed Protein Kinase FA Is A
Novel Independent Prognostic Predictor in
Cholangiocarcinoma 47
CHAPTER 6 Proline-Directed Protein Kinase FA Is A
Novel Independent Prognostic Predictor in
Gastric Cancer 67
CHAPTER 7 General Discussion 95
CHAPTER 8 Concluding Remarks 105
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