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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 周綠蘋 | |
| dc.contributor.author | Wen-Yea Yau | en |
| dc.contributor.author | 姚文雅 | zh_TW |
| dc.date.accessioned | 2021-06-16T08:29:26Z | - |
| dc.date.available | 2017-02-25 | |
| dc.date.copyright | 2014-02-25 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-01-07 | |
| dc.identifier.citation | [1] Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94:153-6.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58758 | - |
| dc.description.abstract | 肝癌是目前世界上死亡率最高的癌症之一且預後較差，B型肝炎病毒感染是肝癌發展中的最主要的致病因子，已有報導指出在許多癌症中腫瘤相關抗原及自體抗體可以成為潛力的生物標誌，藉由鑑定腫瘤發展早期引發免疫反應的腫瘤相關抗原可做為癌症早期診斷並發展出治療方法，因此我們利用免疫蛋白體學方法鑑定與B型肝炎病毒相關肝細胞癌病人血清反應的腫瘤相關抗原，將二維膠片上有免疫反應的蛋白點切下並利用奈流液相層析質譜儀分析，結果顯示總共鑑定到16個腫瘤相關抗原，進一步表現重組蛋白進行免疫墨點法及酵素結合免疫分析，其中異質核核醣核蛋白L是一個顯著的腫瘤相關抗原(60%)，N端富含甘胺酸區域具有引起免疫反應的最主要抗原決定區，在B型肝炎病毒相關肝細胞癌病人中自體抗體有顯著性增高的現象，並且與腫瘤大小與存活率有高度相關性。此外也發現在肝癌組織中異質核核醣核蛋白L有高量表達的現象，在細胞實驗中發現減少異質核核醣核蛋白L表現導致細胞生長、移動及轉移受到抑制。由本研究顯示異質核核醣核蛋白L的富含甘胺酸區域具有最主要抗原決定區並且可以成為一個偵測B型肝炎病毒相關肝細胞癌病人的潛力生物標記，此外，在癌化過程中異質核核醣核蛋白L可能是藉由促進肝癌細胞生長及惡化。 | zh_TW |
| dc.description.abstract | Hepatocellular carcinoma (HCC) is associated with a poor prognosis and remains one of the leading causes of cancer death worldwide. Hepatitis B virus (HBV) infection is the most prominent etiologic factor for developing HCC. Tumor-associated antigens (TAAs) and autoantibodies have been reported as potential markers in different cancers. Identification of TAAs capable of eliciting an immune response early in tumor development will lead to early diagnosis of cancer and the development therapeutic approach. Here, we employed an immunoproteomic approach to identify TAAs in the sera of patients with HBV-related HCC (HBV-HCC). Immunoreactive spots were excised from 2-DE and analyzed by nano-LC-MS/MS. This analysis identified 16 HCC-associated antigens, including hnRNP L. The antigenicity of hnRNP L was further validated by immunoblotting and ELISA using recombinant proteins. Autoantibodies against hnRNP L were found in 60% patients with HBV-HCC. Using sera from hnRNP L-positive patients, we found that most of these antibodies recognized glycine-rich region in the N-terminus of hnRNP L. In addition, high titers of autoantibodies against hnRNP L were found in HBV-HCC patients’ sera and were associated with increased tumor size and reduced survival rate. hnRNP L protein was also found highly expressed in HCC tissue. Knockdown of hnRNP L significantly suppressed cell growth, migration, and invasion in vitro. Our results indicate that an N-terminal epitope of hnRNP L is a potential biomarker for the diagnosis of HBV-HCC and show that hnRNP L contributes to HCC progression. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T08:29:26Z (GMT). No. of bitstreams: 1 ntu-103-D95442005-1.pdf: 3796274 bytes, checksum: 9c8179b77fe0d3948a9578a7f355b449 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
中文摘要 ii Abstract iii Abbreviations v Table of Contents viii Chapter I – Overview and Rationale 1 1.1 Liver cancer 2 1.2 Risk factors for the development of HCC 3 1.3 Diagnosis of HCC 6 1.4 Tumor-associated antigens (TAAs) and autoantibodies 8 1.5 Specific aim 14 Chapter II – Autoantibody recognition of an N-terminal epitope of hnRNP L marks the risk for developing HBV-related hepatocellular carcinoma 16 2.1 Introduction 17 2.2 Experimental Procedures 20 Patients and serum samples 20 Cell culture 20 2-DE and 2-D immunoblotting 21 In-gel digestion 22 LTQ OrbiTrap Velos MS analysis and protein identification 22 Cloning and purification of recombinant proteins 23 Competition ELISA 24 Immunoblotting analysis 25 Lentiviral vector-mediated transduction of hnRNP L-specific shRNA 26 Anchorage-independent growth 26 Cell proliferation assay 26 Cell-cycle analysis 27 Wound-healing assay 27 Matrigel invasion assay 28 Statistical analysis 28 2.3 Results 30 TAAs and autoantibodies identification in HBV-related HCC 30 Identification of HBV-HCC-related TAAs by 2-D immunoblotting analysis 30 Analysis of the prevalence of autoantibodies against hnRNP L, lamin and hnRNP B1 31 Serum autoantibodies against hnRNP L-L isoforms 33 Identification of the major epitope of hnRNP L-L 34 Correlation between the epitope titer of hnRNP L-67–88 autoantibodies and the clinical characteristics of HCC patients 36 hnRNP L knockdown in HCC cells inhibits anchorage-independent growth and proliferation by inducing cell-cycle arrest in the G0/G1 phase 38 hnRNP L knockdown inhibits the migration and invasion of HCC cells 39 2.4 Discussion 41 Chapter III –Conclusion and perspectives 46 Conclusion and perspectives 47 List of Tables & Figures 50 References 80 Appendix 87 List of instrument 88 | |
| dc.language.iso | en | |
| dc.subject | B型肝炎病毒 | zh_TW |
| dc.subject | 異質核核醣核蛋白L | zh_TW |
| dc.subject | 血清蛋白體分析技術 | zh_TW |
| dc.subject | 腫瘤相關抗原 | zh_TW |
| dc.subject | 肝細胞癌 | zh_TW |
| dc.subject | 自體抗體 | zh_TW |
| dc.subject | tumor-associated antigens | en |
| dc.subject | hepatitis B virus | en |
| dc.subject | hepatocellular carcinoma | en |
| dc.subject | heterogeneous nuclear ribonucleoprotein L | en |
| dc.subject | serological proteome analysis | en |
| dc.subject | autoantibody | en |
| dc.title | 利用免疫蛋白體學方法鑑定腫瘤相關抗原作為肝細胞癌之生物標記 | zh_TW |
| dc.title | Using an immunoproteomic approach to identify tumor-associated antigens as biomarkers in hepatocellular carcinoma | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 許金川,陳健弘,蔡孟勳,郭敏玲 | |
| dc.subject.keyword | 自體抗體,B型肝炎病毒,肝細胞癌,異質核核醣核蛋白L,血清蛋白體分析技術,腫瘤相關抗原, | zh_TW |
| dc.subject.keyword | autoantibody,hepatitis B virus,hepatocellular carcinoma,heterogeneous nuclear ribonucleoprotein L,serological proteome analysis,tumor-associated antigens, | en |
| dc.relation.page | 88 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-01-08 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
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