2010-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/686899摘要：癌症是全世界婦女健康的重大威脅，每年造成數以千萬計的患者死亡，使得許多的家庭失去它們的妻子，母親和女兒。在所有侵襲婦女的癌症中，卵巢癌具有最高的疾病致死率。因此，對造成卵巢癌惡化的機制進行研究分析，在未來對於卵巢癌的治療與診斷上將有絕大的幫助。卵巢癌是一種複雜的腫瘤，它在病理診斷上有不同的亞型（漿液性，類子宮內膜，粘液性，透明細胞），也可依據不同的惡性度再細分為，低惡性度腫瘤或侵襲性癌。卵巢癌的特點之一是卵巢癌細胞中有很高比例的基因受到損傷，進而造成卵巢癌細胞具有複雜且多樣的基因改變。由於卵巢癌的複雜性，醫學界仍很缺乏對於造成卵巢癌惡化機制的深入研究。在造成卵巢癌惡化的基因了解上，也充滿了相當的困難度與挑戰性，並造成開發新治療方式的瓶頸。本研究計劃將針對造成卵巢癌惡化的基因進行研究，我們希望透過此一研究計畫找到台灣婦女卵巢癌轉移可能特有的基因變異。我們將收集卵巢癌患者的腹水、及切取原發部位卵巢癌及四處腹腔轉移卵巢癌檢體，我們將利用收集卵巢癌患者手術時取出的腫瘤檢體，從中提取腫瘤組織的基因遺傳物質(DNA及RNA)。由於比較分析的必要，我們也將需要抽取卵巢癌患者的周邊血液，從中提取患者的正常基因遺傳物質(DNA)。我們預計收集20位病人之檢體，取得病人手術時切下的新鮮檢體，再抽取其 DNA及RNA，再進行進一步分析。此研究計劃的優點是整合系統生物學（基因組學，轉錄，對位性基因體），它將對完整的了解卵巢癌提供一個開始，且這種分析將為致癌的過程提供一個更精準的角度。大多數的研究著重於非基因或基因體在癌症生物學上的改變，卻未整合細胞的基因及其調控的複雜性。此一前瞻性的試驗計畫將在腫瘤分析上建立新的標準，高速產出技術將可以在腫瘤生物學的不同層面上進行快速分析。此外，由本研究得到的數據將啟發我們對腫瘤生物學中轉移過程的複雜現象的理解。轉移過程的複雜性不只是基因表現的修飾更包含基因體高程度的不穩定性及與微環境的互動所造成的基因外調控。本研究將對致癌基因體的修飾所導致的轉移進行整合性的分析。我們會嚴格篩選相同腫瘤類型及相近臨床特徵的病人，以避免因不同腫瘤所造成的異質性，我們將專注於獲得以下重要的數據：-基因表現-微核糖核酸概況-基因組的變化：基因數變化-基因外的概況：去氧核醣核酸甲基化和組蛋白轉譯後的狀態透過此一研究計畫我們希望找到台灣婦女卵巢癌轉移可能特有的基因變異及其調控，特別是微核醣核酸調控腫瘤進展的可能分子機制，以期對於未來卵巢癌的發生、預防及治療提供正確的研究方向。<br> Abstract: Ovarian cancers are one of the leading causes of death among womenworldwide and in Taiwan. Many families lost their mother, daughter, and wives. Themortality of ovarian cancers is due to the development of metastatic diseases.However, current studies have not provided a comprehensive glimpse of detailedmechanisms and/or pathways governing the progression of ovarian carcinoma.Ovarian cancer is a heterogeneous entity with different histological subtypes(serous, endometrioid, mucinous, clear cell) and invasive behavior (borderline tumors,invasive carcinoma). Ovarian carcinoma is characterized by a high degree of geneticdamages and multiple genetic alterations. This heterogeneity has made theunderstanding of the molecular mechanism of carcinogenesis and cancer progressionchallenging.We propose to investigate the possible genomic mechanisms that lead toovarian carcinoma progression. We will enroll 20 advanced stage ovarian carcinomapatients into this study. Each patient will contribute the ascitic fluids (if any), and tumorsamples from the primary site, four different quadrant of the peritoneal implants (RLQ,RUQ. LLQ. LUQ) resected from the surgical procedures. DNA and RNA extractedfrom the tumor samples will be subjected to analysis. For the necessity of the baselineconstruction, we will also collect the peripheral blood from the patient and extract thegenomic DNA from the peripheral blood.The strength of this proposal is ensured by the collaborative effort of integratingtechnologic platforms of systems biology (genomics, transcriptomics, epigenomics). Itwill provide an initiative for a comprehensive and multidisciplinary understanding ofovarian carcinoma. This analysis will provide a more accurate and dynamic vision ofoncogenomic processes. This pilot project not only will set new standards in terms oftumor analysis, but also will lead to the development of tools that will allow theintegration of all different data set on a particular tumor to be able to predict outcome.This study will allow an integrated analysis of the oncogenomic modifications leadingto metastasis. Through a rigorous selection of patients displaying the same tumor typeand comparable clinical characteristics to avoid heterogeneity induced by tumorsdifferences, we will be able to focus on combining all the data obtained:-Gene expression-Micro-RNA profile-Genomic alterations: Copy number variations-Epigenetic profile: DNA methylation and histone post translationalstatus.卵巢癌去氧核醣核酸甲基化組蛋白轉譯Ovarian cancerDNA methylationhistone post translation