以系統生物學分析方法篩選與驗證癌轉移相關基因

多數癌症己被界定為基因變異所造成的疾病(genetic disorder)，且有90%的癌症病人因癌轉移而死亡，而癌轉移的發生不僅僅單就單一基因及單一傳遞路徑來探討，應以全面性的角度來探討。本研究針對癌細胞轉移為主要方向，整合公開資料庫生物晶片資料經統計分析，預測出98個具有轉移的潛力基因以及104個抑制轉移基，並利用in vitro以及Functional Assay，結合臨床上的病患檢體加以對照分析，成功證實其中三個基因與細胞侵襲有關，且其中一個基因與上皮-間質化有關，更增加本研究預測準確性。本研究也利用了本實驗室開發之"基因調控網路與反應路徑系統"，找出具有差異性表現的癌轉移相關路徑，並結合上述產出之癌轉移相關的潛力基因群，觀察在生物體內的反應路徑(pathway)，以了解促癌轉移潛力基因上下游調控機制。對於未來研究，可參考此癌轉移表現量高的路徑，製造直接作用在膜上的小分子藥物，從源頭阻斷癌轉移可能路徑。

關鍵字

癌轉移；基因調控網路；子宮內膜異位症

並列摘要

Metastasis at distant sites is a multiple-step process which requires the accumulation of altered expression of many different genes. It is also the main cause contributing high mortality of cancer. Moreover, previous study has defined that cancer is genetic disorder in entity. Here in this study, we developed a novel approach to obtain Metastatic Related Genes with the combination of genome-wide measures of gene expression and pathway-based expression analysis. Our group have obtained a group of Metastatic Promoting Genes (MPG) and Metastatic Suppressing Genes (MSG) by comparing the gene expression profiling from metastatic tumors, benign tumors, ectopic ovarian endometrium, eutopic endometrium microarrays. Firstly, we validated these Metastatic Related Genes by RT-PCR in different specimens from metastatic cancer and benign cancer patients respectively. Secondly, we identified these genes which have the function of invasive and metastatic competence by conducting invasion assay in vitro. Meanwhile, we also conducted pathway-based expression analysis which combined microarray gene expression data, gene network and gene ontology to identify the roles of these Metastatic Related Genes. Result has revealed that part of MPG are consistent with our prediction and has validated these MPG have invasive and metastatic capabilities. In the future, those Metastatic Related Genes combining with metastatic-related pathway could effectively differentiate the potential tendency for tumor to metastasize and could facilitate the potential therapeutic drug compound development

並列關鍵字

Metastasis ； Endometriosis ； Pathway-based expression analysis

參考文獻

"The Gene Ontology (GO) project in 2006." Nucleic Acids Res 34(Database issue): D322-326.

Ahmad, A., J. F. Marshall, et al. (1997). "Modulation of human stromelysin 3 promoter activity and gene expression by human breast cancer cells." Int J Cancer 73(2): 290-296.

Alikunju, S. and S. Pillarisetti (2006). "Selected players in the inflammation cascade and drugs that target these inflammation genes against metastasis." Anticancer Agents Med Chem 6(5): 461-468.

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Bracke, M. E., F. M. Van Roy, et al. (1996). "The E-cadherin/catenin complex in invasion and metastasis." Curr Top Microbiol Immunol 213 ( Pt 1): 123-161.

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以系統生物學分析方法篩選與驗證癌轉移相關基因

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