請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17563完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 于明暉(Ming-Whei Yu) | |
| dc.contributor.author | Yu-Huei Lien | en |
| dc.contributor.author | 連玉惠 | zh_TW |
| dc.date.accessioned | 2021-06-08T00:21:30Z | - |
| dc.date.copyright | 2013-09-24 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-07-22 | |
| dc.identifier.citation | 1. Jemal A. Global cancer statistics (vol 61, pg 69, 2011). CA: A Cancer Journal for Clinicians 2011;61(2):134-134.
2. Wang JH, Changchien CS, Hu TH, et al.The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma - Survival analysis of 3892 patients. European Journal of Cancer 2008;44(7):1000-6. 3. Perz JF, Armstrong GL, Farrington LA, et al.The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. Journal of Hepatology 2006;45(4):529-538. 4. Bruix J, Sherman M, Practice Guidelines Committee AAftSoLD. Management of hepatocellular carcinoma. Hepatology 2005;42(5):1208-36. 5. El-Serag HB. Hepatocellular Carcinoma. New England Journal of Medicine 2011;365(12):1118-1127. 6. Chen CC, Yang SY, Liu CJ, et al. Association of cytokine and DNA repair gene polymorphisms with hepatitis B-related hepatocellular carcinoma. International Journal of Epidemiology 2005;34(6):1310-1318. 7. Yu MW, Gladekyarborough A, Chiamprasert S, et al. Cytochrome P450 2E1 and glutathione S-transferase M1 polymorphisms and susceptibility to hepatocellular carcinoma. Gastroenterology 1995;109(4):1266-1273. 8. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012;142(6): 1264-1273.e1 9. Li S, Qian J, Yang Y, et al. GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers. PLoS Genetics 2012;8(7):e1002791. 10. Henderson JM, Sherman M, Tavill A, et al. AHPBA/AJCC consensus conference on staging of hepatocellular carcinoma: consensus statement. HPB (Oxford) 2003;5(4):243-50. 11. Llovet JM. Updated treatment approach to hepatocellular carcinoma. Journal of Gastroenterology 2005;40(3):225-235. 12. Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. Journal of Cancer Research and Clinical Oncology 2004;130(7):417-422. 13. Trevisani F, D'Intino PE, Morselli-Labate AM, et al. Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. Journal of Hepatology 2001;34(4):570-575. 14. Okuda K. Early recognition of hepatocellular carcinoma. Hepatology 1986;6(4):729-738. 15. Yu MW, Yeh SH, Chen PJ, et al. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men. Journal of the National Cancer Institute 2005;97(4):265-72. 16. Yang HI, Yuen MF, Chan HL, et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score. Lancet Oncology 2011;12(6):568-74. 17. Herceg Z, Paliwal A. Epigenetic mechanisms in hepatocellular carcinoma: How environmental factors influence the epigenome. Mutation Research/Reviews in Mutation Research 2011;727(3):55-61. 18. Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature 2005;435(7043):834-838. 19. Zhang XY, Zhang EJ, Ma ZY, et al. Modulation of hepatitis B virus replication and hepatocyte differentiation by microRNA-1. Hepatology 2011;53(5):1476-1485. 20. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993;75(5):843-854. 21. Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nature Reviews Cancer 2006;6(4):259-269. 22. Frankel LB, Christoffersen NR, Jacobsen A, et al. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. Journal of Biological Chemistry 2008;283(2):1026-1033. 23. Calin GA. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. New England Journal of Medicine 2006;355(5):533-533. 24. Ng EKO, Chong WWS, Jin H, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 2009;58(10):1375-1381. 25. Zhang J, Yang Y, Yang T, et al. microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity. British Journal of Cancer 2010;103(8):1215-1220. 26. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy of Sciences of the United States of America 2008;105(30):10513-10518. 27. Chen X, Ba Y, Ma LJ, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Research 2008;18(10):997-1006. 28. Zhou J, Yu L, Gao X, et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. Journal of Clinical Oncology 2011;29(36):4781-4788. 29. Liu AM, Yao TJ, Wang W, et al. Circulating miR-15b and miR-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open 2012;2(2). 30. Yu MW, Shih WL, Lin CL, et al. Body-mass index and progression of hepatitis B: a population-based cohort study in men. Journal of Clinical Oncology 2008;26(34):5576-82. 31. Wu CF, Yu MW, Lin CL, et al. Long-term tracking of hepatitis B viral load and the relationship with risk for hepatocellular carcinoma in men. Carcinogenesis 2008;29(1):106-12. 32. Irizarry RA, Hobbs B, Collin F, et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003;4(2):249-64. 33. Whittaker S, Marais R, Zhu AX. The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 2010;29(36):4989-5005. 34. Su H, Yang JR, Xu T, et al. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Research 2009;69(3):1135-1142. 35. Stoorvogel W. Functional transfer of microRNA by exosomes. Blood 2012;119(3):646-648. 36. Thery C, Regnault A, Garin J, et al. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. Journal of Cell Biology 1999;147(3):599-610. 37. Raposo G, Nijman HW, Stoorvogel W, et al. B lymphocytes secrete antigen-presenting vesicles. Journal of Experimental Medicine 1996;183(3):1161-72. 38. Blanchard N, Lankar D, Faure F, et al. TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. Journal of Immunology 2002;168(7):3235-41. 39. van Niel G, Raposo G, Candalh C, et al. Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 2001;121(2):337-49. 40. Mears R, Craven RA, Hanrahan S, et al. Proteomic analysis of melanoma-derived exosomes by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Proteomics 2004;4(12):4019-31. 41. Valadi H, Ekstrom K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biology 2007;9(6):654-9. 42. Rabinowits G, Gercel-Taylor C, Day JM, et al. Exosomal microRNA: a diagnostic marker for lung cancer. Clinical Lung Cancer 2009;10(1):42-6. 43. Tomimaru Y, Eguchi H, Nagano H, et al. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. Journal of Hepatology 2012;56(1):167-75. 44. Salvi A, Sabelli C, Moncini S, et al. MicroRNA-23b mediates urokinase and c-met downmodulation and a decreased migration of human hepatocellular carcinoma cells. Federation of European Biochemical Societies Journal 2009;276(11):2966-82. 45. Ma KL, He YH, Zhang HY, et al. DNA methylation-regulated miR-193a-3p dictates resistance of hepatocellular carcinoma to 5-fluorouracil via repression of SRSF2 expression. Journal of Biological Chemistry 2012;287(8):5639-5649. 46. Shwetha S, Gouthamchandra K, Chandra M, et al. Circulating miRNAs profile in HCV infected serum: novel insight into pathogenesis. Scientific Reports 2013;3:1555. 47. Li QJ, Zhou L, Yang F, et al. MicroRNA-10b promotes migration and invasion through CADM1 in human hepatocellular carcinoma cells. Tumour Biology 2012;33(5):1455-65. 48. Xu T, Zhu Y, Xiong Y, et al. MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology 2009;50(1):113-21. 49. Zhang JF, He ML, Fu WM, et al. Primate-specific microRNA-637 inhibits tumorigenesis in hepatocellular carcinoma by disrupting signal transducer and activator of transcription 3 signaling. Hepatology 2011;54(6):2137-2148. 50. Murakami Y, Tamori A, Itami S, et al. The expression level of miR-18b in hepatocellular carcinoma is associated with the grade of malignancy and prognosis. BMC Cancer 2013;13:99. 51. He YH, Cui Y, Wang W, et al. Hypomethylation of the hsa-miR-191 locus causes high expression of hsa-mir-191 and promotes the epithelial-to-mesenchymal transition in hepatocellular carcinoma. Neoplasia 2011;13(9): 841-53. 52. Son JW, Kim YJ, Cho HM, et al. MicroRNA expression profiles in Korean non-small cell lung cancer. Tuberculosis and Respiratory Diseases 2009;67(5):413-421. 53. Kormish JD, Sinner D, Zorn AM. Interactions between SOX factors and Wnt/beta-catenin signaling in development and disease. Developmental Dynamics 2010;239(1):56-68. 54. Hur W, Rhim H, Jung CK, et al. SOX4 overexpression regulates the p53-mediated apoptosis in hepatocellular carcinoma: clinical implication and functional analysis in vitro. Carcinogenesis 2010;31(7):1298-307. 55. Guo X, Yang M, Gu H, et al. Decreased expression of SOX6 confers a poor prognosis in hepatocellular carcinoma. Cancer Epidemiology 2013; 10.1016/j.canep.2013.05.002. 56. Allen-Jennings AE, Hartman MG, Kociba GJ, et al. The roles of ATF3 in liver dysfunction and the regulation of phosphoenolpyruvate carboxykinase gene expression. The Journal of Biological Chemistry 2002;277(22):20020-5. 57. Srisuttee R, Koh SS, Park EH, et al. Up-regulation of Foxo4 mediated by hepatitis B virus X protein confers resistance to oxidative stress-induced cell death. International Journal of Molecular Medicine 2011;28(2):255-60. 58. Buscaglia LEB, Li Y. Apoptosis and the target genes of miR-21. Chinese Journal of Cancer 2011;30(6):371. 59. Meng F, Henson R, Wehbe-Janek H, et al. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007;133(2):647-58. 60. Toiyama Y, Takahashi M, Hur K, et al. Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. Journal of the National Cancer Institute 2013;105(12):849-859. 61. Hennessey PT, Sanford T, Choudhary A, et al. Serum microRNA biomarkers for detection of non-small cell lung cancer. PLoS One 2012;7(2):e32307. 62. Hu Z, Dong J, Wang LE, et al. Serum microRNA profiling and breast cancer risk: the use of miR-484/191 as endogenous controls. Carcinogenesis 2012;33(4):828-34. 63. Luo X, Burwinkel B, Tao S, et al. MicroRNA signatures: novel biomarker for colorectal cancer? Cancer Epidemiology, Biomarkers and Prevention 2011;20(7):1272-86. 64. Li LM, Hu ZB, Zhou ZX, et al. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. Cancer Research 2010;70(23):9798-807. 65. Xu J, Wu C, Che X, et al. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Molecular Carcinogenesis 2011;50(2):136-42. 66. Callari M, Dugo M, Musella V, et al. Correction: Comparison of microarray platforms for measuring differential microRNA expression in paired normal/cancer Colon Tissues. PLoS One 2013;8(5). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17563 | - |
| dc.description.abstract | 研究背景與目的：過去研究已經指出microRNAs (miRNAs) 透過使癌症相關基因的表現失去調節，參與癌症的形成與細胞分化。此外，從不同組織來的miRNAs可以在週邊血液裡被偵測到。因此，miRNAs具有成為應用在癌症診斷或篩檢介入之生物標記的潛力。本篇研究的目的在於從B型肝炎 (hepatitis B virus, HBV) 帶原者中找出HCC發展相關的特定循環miRNAs，並且探討這些miRNAs作為預測HCC風險之可信賴的新生物標記的可能性。
材料與方法：本篇研究使用巢式病例對照研究 (nested case - control study)，樣本源自於先前已經發表的世代研究。此世代研究在1989-1992年納入2903名HBV帶原者，並且持續追蹤這些研究對象至2009年。病例在以進入研究時間、進入研究年齡以及抽血時間點配對後，再隨機選取出本研究的對照組。本研究分成三個部分：(1) 使用微矩陣分析 (microarray analysis) 比較50名病例與50名對照之miRNAs表現差異，並且以Conditional logistic regression檢定；(2) 以miRNAs的表現為基礎執行路徑分析，以了解其生物上的意義；(3) 使用顯著的miRNAs指標建構HCC風險之預測模式。 結果：我們的微矩陣分析結果顯示79個顯著差異表現於病例和對照組的miRNAs，其中7個miRNAs在3端未轉譯區域預測的結合位置之基因 (miR-191、 miR-193a-3p、miR-23b、miR-3139、 miR-378f、miR-4640-5p以及miR-637) 參與ERK/MAPK、胰島素接受器 (insulin receptor)、mTOR、PI3K/AKT或者Wnt/β-catenin訊息傳導路徑上。最後，我們發現4個miRNA標記加上HBV基因型的組合，能從HBV帶原者中精確辨認出會進展成為HCC病患的高危險群 (AUC曲線下面積 = 0.88；95% 信賴區間 = 0.80-0.95)。 結論：我們發現多個循環的miRNAs顯著相關於HCC風險，推測可能牽涉HBV感染相關的HCC形成。miRNA指標結合已知的病毒血清標記可能會增加預測HCC風險之能力。 | zh_TW |
| dc.description.abstract | Background and aim: Studies have shown that microRNAs (miRNAs) are involved in carcinogenesis and cellular proliferation through dysregulating cancer-related gene expression. In addition, miRNAs from various tissues can be detected in peripheral blood. Therefore, miRNAs exhibit great potential as biomarkers for application in cancer diagnosis or screening for intervention. The aims of this study were to characterize distinctive circulating miRNA profile in relation to HCC development in hepatitis B virus (HBV) carriers, and to address the possibility that miRNAs might be used as promising novel biomarkers for prediction of HCC risk.
Materials and Methods: A nested case-control study was designed within a published cohort of 2903 HBV carriers who were enrolled between 1989-1992, and followed up through 2009. Cases were matched with randomly selected controls on the timing and age at the time subjects involved in this cohort, and the time of collection of the blood sample. This study was divided into three steps: first, microarray analysis comparing 50 cases and 50 controls by using conditional logistic regression; second, pathway analysis based on miRNAs profiling to provide biological insight; third, use of a signature of significant miRNAs to construct predictive model for HCC risk. Results: Our microarray analysis revealed 79 miRNAs that significantly differentially expressed in cases compared with controls, among which 7 miRNAs (miR-191-5p, miR-193a-3p, miR-23b-3p, miR-3139, miR-378f, miR-4640-5p, miR-637) have predictive binding sites within the 3’-untranslated regions of a panel of genes involved in ERK/MAPK, insulin receptor, mTOR, PI3K/AKT, or Wnt/β-catenin signaling. Finally, we found 4 miRNA signatures combined with HBV genotype that accurately discriminated HBV carriers at high risk to progress to HCC (area under receiver operation curve = 0.88；95% confidence interval = 0.80-0.95). Conclusion: We found multiple circulating miRNAs significantly associated with HCC risk, suggesting underlying mechanisms of HBV-related hepatocellular carcinogenesis. A miRNA signature might be used in combination with known viral seromarkers to enhance the accuracy of prediction of HCC risk. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T00:21:30Z (GMT). No. of bitstreams: 1 ntu-102-R00849023-1.pdf: 1127470 bytes, checksum: ff2acede2ec8208724bf11a37d078235 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 目 錄
口試委員會審定書…………………………………………………………………...i 誌謝…………………………………………………………………………………...ii 中文摘要…………………………………………………………………………….iii 英文摘要…………………………………………………………………………….iv 前言…………………………………………………………………………………...1 材料與方法…………………………………………………………………………...5 結果…………………………………………………………………………...............8 討論…………………………………………………………………………...............9 參考文獻………………………………………………………………………….....15 附錄 表一………………………………………………………………………………….21 表二………………………………………………………………………………….22 表三………………………………………………………………………………….23 表四………………………………………………………………………………….24 圖一………………………………………………………………………………….25 圖二………………………………………………………………………………….26 補充資料一………………………………………………………………………….27 | |
| dc.language.iso | zh-TW | |
| dc.title | 微型核醣核酸表現之微陣列分析和預測慢性B型肝炎病患罹患肝細胞癌 | zh_TW |
| dc.title | Microarray Analysis of MicroRNA Expression for Prediction of Hepatocellular Carcinoma in Chronic Hepatitis B Patients | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鄭尊仁教授(Tsun-Jen Cheng),莊雅惠(Ya-Hui Chuang),林志陵(Chih-Lin Lin) | |
| dc.subject.keyword | miRNAs,HCC,生物標記,路徑分析,AUC, | zh_TW |
| dc.subject.keyword | miRNAs,HCC,biomarker,pathway analysis,AUC, | en |
| dc.relation.page | 30 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2013-07-23 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-102-1.pdf 未授權公開取用 | 1.1 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。