鑑別可應用在病理與臨床之肺腺癌與鱗狀上皮細胞肺癌的生物標記

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姓名

詹修華(Hsiu-hua Chan) 查詢紙本館藏

畢業系所

系統生物與生物資訊研究所

論文名稱

鑑別可應用在病理與臨床之肺腺癌與鱗狀上皮細胞肺癌的生物標記
(Identification of biomarkers for differentiating adenocarcinoma and squamous cell carcinoma of lung for pathological and clinical application)

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摘要(中)

在全世界肺癌是造成癌症致死率很高的首要原因,主要型態包括小細胞肺癌(~15%)與非小細胞肺癌(~85%),非小細胞肺癌又可以分為肺腺癌, 鱗狀上皮細胞肺癌和大細胞肺癌,其中以肺腺癌在台灣佔大多數，在不同類別的肺癌裡，分別都使用不同的化療用藥，造成的副作用與預後情形也都不一樣。分化完全的肺腺癌和鱗狀上皮細胞肺癌通常只需要經由蘇木精和伊紅染色法之後經由肉眼判斷癌細胞型態與角質化與否便能有效辨別腫瘤細胞，但是分化不全的非小細胞肺癌卻很難由肉眼判斷。在病理與臨床應用上，NKX2-1與KRT5/6是目前分別被應用在輔助鑑別分化不全的非小細胞肺癌裡的肺腺癌和鱗狀上皮細胞肺癌上的病理標記。經由研究發現NKX2-1與KRT5/6目前對於在鑑別分化不全之小樣本非小細胞肺癌上效果也並不是相當成功。因此發展出能夠有效鑑別分化不全之小樣本非小細胞肺癌的生物病理標記是當前刻不容緩的研究議題。運用生物資訊與高通量篩選平台及整合功能性生物分析工具並藉由微陣列生物晶片分析及免疫染色法我們最後找出4種生物標記分別為KRT13, ADH7, CALML3和FOXA2來鑑別分化不全之小樣本非小細胞肺癌，希望在病理與臨床應用上，對於非小細胞肺癌診斷、療效評估與化學治療方法的選擇能夠有新的突破。

摘要(英)

Lung cancer is the leading cause of cancer deaths in the worldwide. The main tumor type includes small cell lung cancer (SCLC ~15% of all lung cancers) and non-small cell lung cancer (NSCLC ~85% of all lung cancers), NSCLC can be classified in adenocarcinoma (AD), squamous-cell carcinoma (SCC), large-cell lung cancer (LCC). Among them, the majority of lung cancer is AD in Taiwan. The different chemotherapy therapeutic drugs can cause the different side effect and prognosis in different kind of lung cancer. Well differentiated AD and SCC can be identify effectively through tumor type or have cytokeratin or not and poorly differentiated AD and SCC is hardly to distinguish by using Hematoxylin & Eosin immunohistochemistry. In pathology and clinical application, NKX2-1 and KRT5/6 are a biomarker, applied to identify poorly differentiated AD and SCC. It is discovered that NKX2-1 and KRT5/6 identify poorly differentiated AD and SCC not very successfully by some research. Therefore, the development of biomarkers can whether effectively identify small samples of poorly differentiated NSCLC or not is currently pressing research issues. Using biological information and high-throughput platform technology, we found 4 biomarkers, including KRT13, ADH7, CALML and FOXA2, may apply to identify small samples of poorly differentiated AD and SCC. We hope it can raise a possibility for the pathology and clinical aspect in the identification of novel molecular markers for disease diagnosis, prognosis, and therapy selection.

關鍵字(中)

★ 肺腺癌
★ 鱗狀上皮細胞肺癌
★ 非小細胞肺癌
★ 分化不全
★ 生物標記
★ 免疫染色法

關鍵字(英)

★ adenocarcinoma of lung
★ squamous cell carcinoma of lung
★ non-small cell lung cancer
★ poorly differentiated
★ biomarker
★ immunohistochemistry

論文目次

Chapter 1 Introduction………………………………………………...………….……………1
Chapter 2 Method and materias…….………………………………..….……….…………….3
2.1 Microarray data analysis…………………………………………..……..……………...3
2.2 Tumor tissue samples and tissue microarray construction…………..….…….…….…...4
2.3 Immunohistochemistry and antibodies…………….………………………....…………4
2.4 Evaluation of immunohistochemical staining……………………...………...….………5
2.5 Statistical analysis…………………………….……………………………...……….....9
Chapter 3 Result…………………………………..……………………………………….….10
3.1 Microarray analysis of AD and SCC…………………………………………………...10
3.2 Immunohistochemical evaluation of candidate genes protein expression on well differentiated NSCLC……………………………………………………………………...22
3.3 Immunohistochemical evaluation of candidate genes protein expression on TMA for lung cancer…………………………………………………………………………………27
3.4 Statistic evaluation of IHC staining results on TMA for lung cancer………....……….36
Chapter 4 Discussion……..…………………………………..………………………………39
Reference…………………...……………...…………………………………………..……..42
Appendix…………………………………….……………………………………….……….45

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指導教授

蘇立仁(Li-jen Su)

審核日期

2014-8-28

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