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系統識別號 U0026-2410201810301200
論文名稱(中文) 探討microRNA-29a於人體肝癌中所扮演的角色:統合分析研究
論文名稱(英文) Role of microRNA-29a in human hepatocellular carcinoma: a meta-analysis
校院名稱 成功大學
系所名稱(中) 分子醫學研究所
系所名稱(英) Institute of Molecular Medicine
學年度 107
學期 1
出版年 107
研究生(中文) 吳姿璿
研究生(英文) Tz-Shiuan Wu
學號 T16051016
學位類別 碩士
語文別 中文
論文頁數 48頁
口試委員 指導教授-張定宗
召集委員-楊孔嘉
口試委員-吳毅晉
中文關鍵字 hepatocellular carcinoma  miR-29a  統計整合分析  生物標記  腫瘤抑制 
英文關鍵字 hepatocellular carcinoma  miR-29a  meta-analysis  tumor suppressor  biomarker 
學科別分類
中文摘要 肝癌(hepatocellular carcinoma, HCC)為目前世界最常見的癌症之一,也是癌症致死率排名第三名的癌症。通常大多數的肝癌病患都在末期時才被確診,因而容易錯過了治療的黃金時期,且肝癌的癌化與轉移速度很快,故若能找到一個早期的、非侵入性的臨床標記物(biomarker)也變得更加重要。
小分子核糖核酸-29a (microRNA-29a;miR-29a)為第一個被發現與癌症有關的小分子核糖核酸。近幾年很多文獻都曾報導過miR-29a與很多實質固態瘤(solid cancer)是有相關性的。然而肝癌與miR-29a之間的相關性卻鮮少被提及,故在本篇研究,我們會以統合分析研究(meta-analysis)去針對HCC與miR-29a之間的相關性進行統計分析,探討miR-29a於肝癌中所扮演的角色。
我們從文獻搜尋的瀏覽器找出的7,464篇研究中,最終再根據我們所設定的標準去篩選出9篇研究來進行統計分析。從文獻中取得相關資訊進行統計,其中高度表現miR-29a的病患中,共有282個人存活、295個人死亡,而低度表現miR-29a的患者中,共有215個人存活、383個人死亡。其餘沒有顯示人數之文獻,我們會直接以作者所提供的勝算比(odds ratio)進行分析。
根據統合分析結果指出,肝臟組織中表現低量miR-29a之患者,具有較高的風險發生肝癌,其勝算比為3.375,95%信賴區間為1.884-6.046,P值小於0.0001。而在死亡率與miR-29a表現量的分析當中,肝臟組織中表現低量miR-29a之患者,有較高的風險發生死亡,其勝算比為1.981,95%信賴區間為1.513-2.594,P值小於0.0001。
然而在我們出版誤差(publication bias)的分析當中,HCC與死亡率的分析皆各有三篇文獻沒有落在標準範圍中,故我們將其移除,移除後之勝算比為2.984,95%信賴區間為1.606-5.544,P值為0.001,仍顯示高度風險。而在死亡率與miR-29a的分析中也有三篇文獻之出版誤差不在扇形的範圍中,移除後之勝算比為1.733,95%信賴區間為1.236-2.431,P值為0.001,結果也與移除前相同。因此我們認為肝臟組織中表現低量miR-29a是可以做為一個HCC的發生以及預後較差的預測因子。
英文摘要 Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and the third leading cause of cancer-related death worldwide. However, most of HCC patients were diagnosed when enter the late stage and miss the chance of treatment. Therefore, to figure out a biomarker of HCC is important for therapy. MicroRNA-29a (miR-29a) is the first cancer-related miRNA which was found in 2001 in HeLa cell. In recent year, miR-29a have been reported that it is associated with many types of cancer. However, there are not many study mention the correlation between HCC and miR-29a. Therefore, in this study, we collect the study about HCC and miR-29a, and use statistical analysis software to observe the correlation between HCC/overall survival and miR-29a with large cohort. Nine of the 7,464 studies, which were searched from EMBASE, Google scholar, and PubMed, were selected for the meta-analysis.
After the systematic meta-analysis, low levels of miR-29a in tissues performed high risk in development of HCC and poor prognosis (HCC: OR=3.375, 95% Confidence interval (IC)=1.884-6.046, P<0.0001; prognosis: OR=1.981, 95% IC=1.513-2.594, P<0.0001). Three studies were excluded after the analysis of publication bias. There are no significant different exist (HCC: OR=2.984, 95% IC= 1.606-5.544, P=0.001; prognosis: OR=1.733, 95% IC=1.236-2.431, P=0.001) after correction of publication bias. In conclusion, we thought miR-29a might be a potential biomarker of HCC, which could predict poor prognosis and development of HCC.
論文目次 中文摘要………………………………………………………I
英文延伸摘要 ………………………………………………III
致謝 ………………………………………………………XXI
壹、緒論 (Introduction) ……………………………………1
一、肝癌……………………………………………………1
1. 造成肝癌的原因………………………………………………1
2. 肝癌的偵測方法………………………………………………6
3. 肝癌的診斷……………………………………………………8
4. 肝癌的臨床分期………………………………………………8
5. 肝癌的治療……………………………………………………9
二、microRNA……………………………………………13
1. miRNA與其標的mRNA之間的相互作用…………………14
2. miRNA的調控 ………………………………………………15
3. miRNA於癌症中所扮演的角色 ……………………………17
三、 miR-29家族…………………………………………19
四、 miR-29a與肝癌目前之研究 ………………………21
貳、材料與方法(Material & Method) ……………………22
一、 文獻搜尋……………………………………………22
二、 納入分析之條件……………………………………22
三、 資料收集……………………………………………22
四、 統計分析……………………………………………23
參、結果(Result) …………………………………………24
一、文獻的選擇 …………………………………………24
二、文獻分類 ……………………………………………24
三、 miR-29a與HCC以及存活率之間的相關性………25
四、 miR-29a與HCC……………………………………25
肆、討論 (Discussion) ……………………………………28
伍、 參考文獻 (Reference) ………………………………29
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