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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90230完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄭文芳 | zh_TW |
| dc.contributor.advisor | Wen-Fang Cheng | en |
| dc.contributor.author | 王彥涵 | zh_TW |
| dc.contributor.author | Yen-Han Wang | en |
| dc.date.accessioned | 2023-09-24T16:07:07Z | - |
| dc.date.available | 2023-11-09 | - |
| dc.date.copyright | 2023-09-23 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-08-08 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90230 | - |
| dc.description.abstract | 研究背景：超過一半的卵巢癌患者被診斷時已為晚期 (第三期和第四期)而致存活率低且多數患者會經歷復發。近年使用標靶藥物PARP抑制劑的維持性療法，於具有BRCA基因變異或同源重組修復缺失（homologous recombination deficiency, HRD）之漿液型腺癌（serous carcinoma）患者可顯著延長無惡化存活期（progression free survival），且這群有基因突變的患者相比沒有的患者對鉑類（platinum）化合物的化療敏感度（platinum sensitivity）較高且無惡化存活期較長。但是目前沒有針對台灣卵巢癌患者同源重組修復（homologous recombination repair, HRR）基因變異之盛行率及其與卵巢癌預後相關性的研究。
研究目的：探討台灣卵巢癌患者之腫瘤同源重組基因變異對疾病預後的相關性。 研究方法：對手術取出之病患腫瘤組織進行病理分析及使用次世代定序檢測是否具有本實驗設計之HRR基因檢測套組內含之基因突變，並結合患者臨床資料分析疾病預後與基因突變的相關性。 研究結果：本研究收集共318名卵巢癌患者中，包含BRCA在內之HRR基因突變在177名漿液性腺癌中佔25.4%，在141名非漿液性卵巢癌中僅佔7.8%，此差異達到統計顯著。在漿液性腺癌中，有HRR基因突變者比起沒有突變者有更高的比例對鉑類化合物有顯著較高的化療敏感度和較長的無惡化存活期和整體存活期（overall survival）。在Cox 多變項迴歸分析下，漿液性腺癌中有HRR基因突變者其復發風險為沒有此突變者的0.64倍（95%信賴區間：0.42-0.98），死亡風險為沒有此突變者的0.54倍（95%信賴區間：0.32-0.90）差異皆達統計顯著。非漿液性卵巢癌中，有無HRR基因突變於化療敏感度、無惡化存活期和整體存活期、復發風險和死亡風險皆沒有顯著差異。 結論：根據研究結果，在漿液性腺癌患者中，HRR基因突變是顯著的預後因子（prognostic factor）。而在非漿液性卵巢癌患者中，是否具有HRR基因突變對化療敏感度和疾病預後沒有顯著影響。未來仍需追蹤這些患者使用PARP抑制劑的治療反應與基因突變之相關性。 | zh_TW |
| dc.description.abstract | Background:Epithelial ovarian cancer (EOC) patients are mostly diagnosed at an advanced stage with poor prognosis. Maintenance therapy with agent such as poly (ADP-ribose) polymerase inhibitors (PARPis) significantly prolong progression free survival in patients with BRCA mutation or homologous recombination deficiency caused by defect in homologous recombination repair (HRR) pathway. The prevalence of HRR genes (including BRCA1/2) mutation in ovarian cancer and the clinical correlations is not well-explored in Taiwanese population.
Purpose:The study aims to evaluate the prevalence of HRR genes mutation of EOC patients in Taiwanese population and to analyze the correlation of HRR genes mutation and clinical outcomes of the EOC patients. Methods:There were 318 EOC patients recruited in the study. The FFPE (formalin fixed paraffin embedded) tissue were analyzed for somatic mutation with a gene panel consists of 23 selected HRR genes, including BRCA1/2. Clinical data including age, cancer stage, residual tumors after debulking surgery, adjuvant treatment and time of recurrence or death were obtained from medical records. Results:Compared to patients with non-serous carcinoma (n=141), patients with serous carcinoma (n=177) had a higher prevalence of HRR genes mutation (25.4% vs. 7.8%, p<0.001), regardless of advanced or early stage (19.6% vs. 13.5%, p=0.176), and HRR genes mutation showed high correlation with platinum-sensitivity (83.9% vs. 69.5%, p=0.029), which was not shown in non-serous carcinoma (54.6% vs. 72.3%, p=0.298). HRR genes mutation in serous carcinoma were associated with longer progression free survival (p=0.004) and overall survival (p<0.001), and lower risk of recurrence (Hazard ratio: 0.64; 95% confidence interval: 0.42-0.98; p=0.039) and death (Hazard ratio: 0.54; 95% confidence interval: 0.32-0.90; p=0.018) by multivariate analysis with Cox proportional hazards model. In non-serous carcinoma, HRR genes mutation showed no significant correlation with survival, risk of recurrence or death. Conclusions:The study confirmed that HRR genes mutation is a prognostic and predictive biomarker in high grade serous carcinoma but not in non-serous carcinoma. PARPis as maintenance therapy in these HRR genes mutated EOC patients is mandatory. | en |
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| dc.description.provenance | Made available in DSpace on 2023-09-24T16:07:07Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iii 英文摘要 v 目錄 vii 圖目錄 ix 表目錄 x 第一章：緒論 1 第一節：研究背景 1 (一) 上皮性卵巢癌概論 1 (二) 上皮性卵巢癌的診斷治療及困境 2 (三) 上皮性卵巢癌的風險及預後因子 6 (四) 上皮性卵巢癌的標靶治療與精準醫療(Precision Medicine) 10 (五) 同源重組修復（Homologous Recombination Repair, HRR） 14 (六) 同源重組修復缺失(Homologous Recombination Deficiency, HRD)檢測 17 第二節：研究的方向與目的 19 第二章：研究方法與材料 20 第一節：患者資料來源及檢體收集 20 第二節：卵巢癌組織DNA萃取 20 第三節：次世代定序（Next generation sequencing, NGS） 21 (一) HRR 基因檢測套組 21 (二) 樣本庫製備(library preparation)、目標基因片段擴增和定序 21 (三) 定序資料輸出及判讀 21 (四) 變異點致病性的判讀 22 第四節：統計分析 22 第三章：研究結果 24 第一節：上皮性卵巢癌患者的臨床特徵 24 第二節：同源重組基因突變與上皮性卵巢癌患者臨床變項的相關性 24 第三節：同源重組基因突變與上皮性卵巢癌患者預後的相關性 24 (一) Kaplan-Meier存活分析 24 (二) Cox迴歸模式分析 25 第四節：比較BRCA和非BRCA同源重組基因突變於漿液性腺癌患者預後之影響 27 第四章：討論 28 第五章：結論 35 第六章：展望 36 參考文獻 55 附錄 80 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 卵巢癌病人HRR基因突變對疾病預後之相關性研究 | zh_TW |
| dc.title | The Correlation of Homologous Recombination Repair (HRR) Genes Mutation and Clinical Outcome of Epithelial Ovarian Cancer Patients | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.coadvisor | 江盈澄 | zh_TW |
| dc.contributor.coadvisor | Ying-Cheng Chiang | en |
| dc.contributor.oralexamcommittee | 李建南 | zh_TW |
| dc.contributor.oralexamcommittee | Chien-Nan Lee | en |
| dc.subject.keyword | 卵巢癌,BRCA,HRR基因檢測套組,預後因子,腫瘤組織,漿液性腺,非漿液性卵巢癌, | zh_TW |
| dc.subject.keyword | ovarian cancer,BRCA,HRR gene panel,prognostic factor,somatic mutation,serous carcinoma,non-serous carcinoma, | en |
| dc.relation.page | 80 | - |
| dc.identifier.doi | 10.6342/NTU202303524 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2023-08-08 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 臨床醫學研究所 | - |
| 顯示於系所單位： | 臨床醫學研究所 | |
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| ntu-111-2.pdf 目前未授權公開取用 | 2.46 MB | Adobe PDF |
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