2011-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/644553摘要：肝癌位居台灣十大癌症死因的首位，常伴隨著肝硬化的發生。外科手術與肝移植是目前治療肝癌最有效的方法，然而手術後經常發生復發與轉移，五年的術後存活率只有30~40%。微型核醣核酸是一個內生性、非編碼RNA，會透過轉譯後修飾來調控基因表現。最近的研究顯示，微型核醣核酸可作為致癌或是抑癌基因，在癌症起始與疾病進展扮演重要角色。許多國內外研究已報導肝癌腫瘤組織相對與旁邊的非腫瘤組織，會有微型核醣核酸的異常表現。雖然已有與癌化相關的微型核醣核酸被報導，但微型核醣核酸之於手術後存活率的資料則相當有限。本研究計畫欲探討微型核醣核酸與肝癌預後的關連性，希望能建立一組微型核醣核酸的分子特徵，來預測肝癌病人的手術後存活率。首先，我們將利用Illumina BeadArray 技術平台對160 位肝癌病人的腫瘤組織進行微型核醣核酸的表現分析。接下來利用Kaplan-Meier 與log-rank 等生物統計方法，分析微型核醣核酸表現量與手術後存活率的相關性。最後，我們將針對這些存活率相關之微型核醣核酸設計功能性試驗，闡明微型核醣核酸的作用機制。透過本計劃的執行，將有機會發展出預測肝癌預後狀況的指標，並且提供有淺力的治療肝癌新標的。<br> Abstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths in Taiwan. HCCnormally develops as a consequence of underlying liver disease and is most often associatedwith cirrhosis. Surgical resection and liver transplantation are current best curative options totreat HCC. However, recurrence or metastasis is quite common in patients who have had aresection and survival rate is 30% to 40% at 5 years postoperatively.MicroRNAs, small non-coding RNA, act as endogenous RNA interference bypost-transcription regulation. Recent studies suggest that microRNAs may act as tumorsuppressors or oncogenes and altered microRNA expression levels may play an important rolein the cancer initiation and progression. Several studies, including ourselves, have shown thatspecific microRNAs are aberrantly expressed in malignant HCC tissues compared to normalcounterpart. Although many microRNA profiling studies were done to diagnosehepatocarcinogenesis, data about prognostic significances for postsurgical survival are verylimited. The main point of this study is to develop a predictive signature for postsurgicalsurvival in HCC patients.Firstly, we will perform microRNA expression profiling of cancerous specimens from 160patients with HCC by using Illumina BeadArray platform. Secondary, Kaplan-Meier methodand log-rank test will be used to analyze the correlation between microRNA expression andsurvival. These survival-related microRNAs may provide a simple profiling method to assistin identifying patients with HCC who are likely to have poor postsurgical survival.Furthermore, functional analysis of these microRNAs will be performed to enhance ourbiological understanding of postsurgical survival of HCC. In conclusion, carrying out thisproject has the opportunity to develop predictor of HCC prognosis and may provide attractivetargets for mechanism-based treatment of HCC.