以系統生物學方法探討肺腺癌抗藥性成因;Systems Biology Approaches to Explore Lung Adenocarcinoma Resistant to Gefitinib

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Title:	以系統生物學方法探討肺腺癌抗藥性成因;Systems Biology Approaches to Explore Lung Adenocarcinoma Resistant to Gefitinib
Authors:	李伯詮;Lee, Po-Chuan
Contributors:	系統生物與生物資訊研究所
Keywords:	肺腺癌;抗藥性;外泌體;Lung Adenocarcinoma;Resistant;exosome
Date:	2020-08-24
Issue Date:	2020-09-02 15:44:36 (UTC+8)
Publisher:	國立中央大學
Abstract:	時至今日，肺癌仍是台灣十大癌症死因之首，其中肺腺癌占大宗。已經有許多文獻對肺腺癌產生gefitinib 抗藥性做出研究。雖然已有部分研究透過分析細胞及外泌體中的遺傳物質找出抗藥性產生的相關訊號通路，但是都僅針對單一一種遺傳物質進行探討。在這裡我們使用兩種因EGFR 突變而導致的人類肺腺癌細胞系，分別為PC-9 和PC-9/IR，其中後者對gefitinib 具有抗藥性，並進行細胞培養。我們從細胞系中分離其外泌體，最後篩選出外泌體中具有顯著表現差異的miRNA、RNA 和蛋白質以及細胞系自身的RNA 等基因產物（fold change > 2 或 < -2），並透過富集分析的方式推測miRNA 下游調控的基因。透過交叉比對外泌體中三種基因產物，我們共找到109 個在基因在外泌體的RNA 和蛋白質有明顯上調的趨勢，其中又有16 個基因的交互作用miRNA 呈現下調，包含IGF2。在KEGG PATHWAY 富集分析中，發現IGF2 與 EEGFR 相關的KEGG 途徑有關。並透過KEA 富集分析表明，IGF2 相較於激酶，更有可能是受到miRNA 導致的上調控。;To date, lung cancer is still the top ten cause of death from cancer in Taiwan, and lung adenocarcinoma accounts for the majority. There have been many studies on the development of gefitinib resistance in lung adenocarcinoma. Although some studies have found out the signaling pathways related to drug resistance through the analysis of genetic material in cells and exosomes, they have only focused on a single genetic material. Here we use two human lung adenocarcinoma cell lines caused by EGFR mutations for cell culture, PC-9 and PC-9/IR, the latter of which is resistant to gefitinib. We isolated exosomes from cell lines, and finally screened out miRNAs, RNAs and proteins with significant performance differences in exosomes, as well as the cell line’s own RNA and other gene products (fold change > 2 or < -2). Through cross-comparison of the three gene products in exosomes, we found a total of 109 genes in exosomes that have a significant up-regulation trend in RNA and protein. Among them, 16 gene interaction miRNAs showed down-regulation, including IGF2.In the KEGG PATHWAY enrichment analysis, IGF2 was found to be related to EEGFR-related enrichment KEGG PATHWAY. And through the KEA enrichment analysis, IGF2 is more likely to be upregulated by miRNA than kinase.
Appears in Collections:	[Institute of Systems Biology and Bioinformatics] Electronic Thesis & Dissertation

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