以功能性基因體合併生物資訊學探討肺腺癌致癌過程之生物反應路徑

Analysis of Biological Pathways in Human Lung Adenocarcinoma Carcinogenesis by Functional Genomics Combined with Bioinformatics

游雅評(Ya-Ping Yu)

指導教授 ： 林綉茹

高雄醫學大學/醫學院/醫學研究所/碩士(2006年)

https://doi.org/10.6832/KMU.2006.00010

摘要

在台灣，肺癌為國人惡性腫瘤罹患率之首，其中，又以肺腺癌(lung adenocarcinoma)所占比例最高1。通常，肺癌患者於初期症狀皆不明顯因此預後不甚理想，故藉由探究肺癌致病機轉並開發早期診斷工具已成為現今最重要的課題之一。因此，本研究目的即以肺腺癌為研究標的並利用微陣列技術合併生物資訊學研究方法，探討肺腺癌與正常肺組織間基因差異性表現情形並藉由分析基因群所參與之路徑，從中推測癌化過程中各路徑所扮演之角色及重要性。由微陣列實驗中得知有3361個基因具差異性表現情形，其中1396個基因為升調節(up regulation；tissue/normal ratio≧2)；1965個基因為降調節(down regulation；tissue/normal ratio≦0.5)，且於cytokine-cytokine receptor interaction)、Focal adhesion及MAPK signaling pathway三大路徑中各包含84、75及66個基因參與(p≦0.05)，為路徑中含差異表現基因數比例最高者。另外，若以基因本體論註解工具分析差異性表現基因群則可得知34%(1162/3361)之基因其功能為cell binding及12%(415/3361)與訊息傳遞作用(signal transduction)相關；進一步，在詳細探討此三大路徑內基因表現情形及其相互間關係後得知，若以focal adhesion此一調控細胞功能與腫瘤起始相關作用為核心路徑則其彼此間具有相互關聯之基因群。基於上述研究結果，吾人期待能早日成功建立肺腺癌之癌化機制並找試尋具潛力之診治分子標記對現今肺癌研究及病患有所助益。

關鍵字

功能性基因體 ； 生物資訊學 ； 肺腺癌 ； 生物反應路徑

並列摘要

In Taiwan, lung cancer ranks first place in incidence rate among all types of malignant tumors. Lung adenocarcinoma is the most common form of lung cancer affecting Taiwanese people. Generally, patients with early stage lung cancer have little or no symptoms. This renders the diagnosis and treatment of most patients with lung cancer too late to obtain promising prognosis. Therefore, the development of diagnostic tools for early detection of lung cancer based on the advances in understanding the mechanism of lung carcinogenesis is a critical issue for lung cancer control. The objectives of this study were to explore genes differentially expressed between lung adenocarcinoma and normal lung tissue, to determine the signaling pathways which the genes might take part in, and to deduce the roles and significance of the signaling pathways in carcinogenesis by means of microarray technique and bioinformatics analyses. The results of microarray showed that there were 3,361 differentially expressed genes. Namely, 1,396 were upregulated (tumor/normal tissue expression ratio≧2) and 1,965 downregulated (tumor/normal tissue expression ratio≦0.5) in lung tumor tissue. The three most-abundant classes of differentially expressed genes were related to cytokine-cytokine receptor interaction (84 genes), focal adhesion (75 genes), and MAPK signaling pathway (66 genes) (p≦0.05). The analyses of gene ontology annotation tool (GOAT) revealed that of these 3,361 genes, 1,162 (34%) and 415 (12%) were involved in functions associated with cell binding and signal transduction, respectively. Moreover, the correlation of expression among genes in the three classes were investigated. It was found that the consideration of focal adhesion as the core pathway could give profound insight to bundles of genes contributing coordinate and integral functions to lung carcinogenesis. Our findings have shed some light on the mystery of mechanism underlying the carcinogenesis of lung adenocarcinoma in modern lung cancer research, and can be also helpful in seeking potential diagnostic/therapeutic markers for patients with lung cancer.

並列關鍵字

functional genomics ； bioinformatics ； lung adenocarcinoma ； biological pathway

參考文獻

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