目的 基于基因芯片数据分析非小细胞肺癌H460细胞株顺铂耐药相关的靶基因及信号传导通路.方法 从基因表达数据库(GEO)下载基因芯片数据,数据预处理后,使用R软件分析H460顺铂耐药细胞株与亲本细胞株中差异表达的基因.运用生物医学信息学方法(基因本体论使用DAVID在线软件进行分析,信号传导通路使用DAVID及Pathway在线软件进行分析)对差异基因的功能和富集的信号通路进行注释,进一步分析H460细胞顺铂耐药调控的关键基因及信号通路.结果 芯片数据分析显示,H460顺铂耐药细胞株较亲本细胞株表达水平显著上调的有7个基因,表达水平显著下调的有27个基因(P均＜0.01).基因本体论分析发现,差异表达的转录本多与肌动蛋白细胞骨架、细胞转移、细胞功能调控以及膜的组成相关.DAVID在线软件分析显示,差异表达上调的基因主要在8条通路中富集,下调基因主要在15条通路中富集.Pathway分析筛选出16条与H460细胞顺铂耐药相关的通路.结论 通过生物信息学方法对GEO基因芯片数据分析,发现了顺铂耐药相关靶基因及信号传导通路.%Objective To screen out the cisplatin resistance-related genes and signal transduction pathways in non-small-cell lung cancer H460 cell line based on GEO.Methods Downloading the gene chip data from the gene expression omnibus (GEO),after data preprocessing,R software was used to analyze the differentially expressed genes of H460 cisplatin-resistant cell line and parental cell line.We also annotated the signal transduction pathways of differentially expressed genes by using biomedical informatics methods (Gene ontology was analyzed by DAVID online software,the signal transduction pathway was analyzed by DAVID and Pathway online software),and further analyzed the key genes and signaling pathways of H460 cisplatin-resistant cells.Results The gene chip data analysis showed that 7 genes were significantly up-regulated in H460 cisplatin-resistant cells,and 27 genes were significantly down-regulated as compared with those of their parental cells (all P ＜ 0.01).Gene ontology found that these differentially expressed transcripts were related to the actin cytoskeleton,cell transfer,cell function regulation,and membrane composition.DAVID online software analysis showed that the genes with up-regulated differential expression were mainly enriched in 8 pathways,and the down-regulated genes were mainly enriched in 15 pathways.In addition,16 pathways were screened out in H460 cisplatin-resistant cells.Conclusion Through the analysis of GEO gene chip data by bioinformatics,we find out the target genes and signal transduction pathways of cisplatiu resistance.
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