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研究生:唐語謙
研究生(外文):Yu-Chien Tang
論文名稱:PLOD2表現與子宮內膜癌在癌化、侵襲及轉移關係之探討
論文名稱(外文):Correlation between PLOD2 expression level and the tumorigenesis and progression of endometrial endometrioid adenocarcinoma
指導教授:余家利余家利引用關係
指導教授(外文):Chia-Li Yu
口試委員:陳祈安
口試委員(外文):Chi-An Chen
口試日期:2013-07-22
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:分子醫學研究所
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:38
中文關鍵詞:子宮內膜癌致癌基因腫瘤生成原膠原離胺酸
外文關鍵詞:Endometrial endometrioid adenocarcinomaoncogenecarcinogenesisPLOD2
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目的:
本研究的目標是找出子宮內膜癌(endometrial endometrioid adenocarcinoma ,EEC)在癌化、侵襲及轉移過程中的相關基因。

材料方法:
手術取得了十個子宮內膜正常的患者(normal endometria, NEM)、十個非典型子宮內膜增生患者(atypical endometrial hyperplasia, AEH)及八十五個子宮內膜癌患者(EEC)的子宮內膜組織檢體。利用GeneChip Array各別分析正常、非典型子宮內膜增生及子宮內膜癌的基因表現圖譜。接著,利用半定量反轉錄聚合酶鍊鎖反應(semi-quantitative reverse transcriptase PCR ,SQ RT-PCR)與定量反轉錄聚合酶鍊鎖反應(real time reverse transcriptase PCR ,RTQ RT-PCR),找出與臨床病理及生存因子之間相關的基因。

結果:
進行微陣列分析之後,利用半定量聚合酶鍊鎖反應,我們挑選出七個候選基因。接著根據先前文獻之報導,挑選其中三個可能為致癌基因的候選者,包含PSAT1、SLC2A1及PLOD2做後續之分析。在八十五個子宮內膜癌患者中,PLOD2在子宮內膜癌(EEC)相對於正常子宮內膜(NEM)及非典型子宮內膜增生(AEH)的表現量顯著較高(p=0.024);而在具較深的肌層侵入、組織分級較高、分化較不完全的子宮內膜癌患者中,也發現了比較高的PLOD2表現量(肌層侵入較深:p=0.041;腫瘤組織分級較高:p=0.039)。此外,其餘兩個基因則在所有分析的臨床病理參數上,都沒有看到其基因表現量與臨床表現具顯著之關係。

結論:
PLOD2可能是子宮內膜癌在癌化過程中扮演著致癌基因的重要角色。然而,其表現量僅與癌化過程及部分病理參數相關,並未與其他臨床表現具明顯之相關性。未來可能需要增大檢體量進一步驗證、或同時再找尋並深入研究其他基因,用以找出在子宮內膜癌的癌化過程、進展及轉移中具關鍵角色,並能用於病患的診斷預後之基因。


Abstract
OBJECTIVE: This study aimed to identify the dysregulated genes involved in the tumorigenesis and progression of endometrial endometrioid adenocarcinoma (EEC).
METHODS: Specimens of endometrial tissues included 10 normal endometria (NEM), 10 atypical endometrial hyperplasia (AEH), and 85 EEC. The expression profiles were compared using GeneChip Array. The gene expression levels were determined by semi-quantitative reverse transcriptase PCR (SQ RT-PCR) in 16 samples and real-time reverse transcriptase PCR (RTQ RT-PCR) in 85 EEC patients. The correlations between the expression of dysregulated genes and clinico-pathologic parameters including survival analysis of EEC were evaluated.
Results: Seven dysregulated genes were first identified through microarray and SQ RT-PCR. Three genes, including PSAT1, SLC2A1, and PLOD2, which were selected according to past reports, underwent subsequent analysis. In our samples, the relative expression levels of PLOD2 (p=0.024) were higher in EEC than in NEM and AEH. The PLOD2 expression levels were higher in EEC with deep myometrial invasion (p=0.041) and higher histologic grade (p=0.039), but had no difference with other clinico-pathologic parameters. The expression levels of two other genes with clinico-pathologic parameters were not different significantly.
Conclusions: PLOD2 might be a dysregulated gene in the tumorigenesis of EEC, but it is not involved in all bio-pathologic features. In the future, we might need to collect more patients to conduct further analysis, or try to investigate other candidates to find genes that may be potential molecular markers for clinical prognosis while detecting the disease and the progression of EEC.


目 錄
口試委員會審定書………………………………………………………………… i
誌謝……………………………………………………………………………… ii
中文摘要……………………………………………………………………… iii
英文摘要………………………………………………………………………… v
前言………………………………………………………………… 1
材料方法………………………………………………………………… 3
結果…………………………………………………………………… 8
討論…………………………………………………………………… 12



參考文獻………………………………………………………………………… 17
附錄……………………………………………………………………………... 34


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