2008-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/694898摘要：近年來微陣列技術被廣範應用於人類各種癌症研究，包括了解癌症相關調控基因的生物機制、建立癌症預後分類法則、開發癌症控制藥物等。進行癌症活體研究是直接對活體採樣得來之癌細胞檢體進行實驗分析，透過活體實驗得以觀察癌細胞在生物體內實際的作用機制。若檢體混雜癌症與非癌症細胞時，利用混雜的mRNA雜合得來的微陣列資料探討與癌症相關的生化機制時，可能會發生誤判或重要產物被稀釋的結果。一般欲純化檢體可透過雷射顯微截取等精密技術為之，但雷射顯微截取技術成本昂貴，截取過程中產生的高熱也容易對檢體造成傷害。為求以低成本且有效的估計檢體中癌細胞各基因之mRNA表現量，本計劃中提出兩種正規化分析法，model-based normalization 與 housekeeping gene normalization。利用混雜癌症與非癌症細胞的檢體所得之微陣列資料進行分析，將正規化前與正規化後各基因之mRNA表現量的估計值進行基因篩選與樣本分類，藉由比較正規化前後所得結果探討所提出正規化方法的可行性。<br> Abstract: In recent years the microarray technology has been widely adopted in cancer research. The applications of microarray technology in cancer research include recapture of regulatory mechanism of oncogenes, development of prognosis classifiers, and drug discovery. Cancer research in vivo means that the experimentation has been conducted on the living tissue, from which the complex biological kinase can be directly observed. However, if the tissue under experiment is a mixture of tumor and non-tumor cells, the observed gene expressions in a microarray might not well represent the mRNA levels from tumor cell. Microscopy combined with laser-assisted microdissection provides a way to reduce the cellular heterogeneity of the tissue but laser microdissection units remain very expensive. In this study, we propose an alternative to estimate the mRNA levels of tumor cells with little cost – to estimate from the microarray gene expression of the mixture tissue via normalization. Two methods are proposed – model-based and housekeeping gene normalizations. The gene expression levels before and after normalization were used to conduct feature selection and classification, respectively, and the results will be compared to assess the validity of the proposed methods.微陣列正規化雷射顯微截取MicroarrayNormalizationLaser Capture Microdissection