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目的:探讨两种酪氨酸激酶抑制剂(TKIs)处理K562细胞的基因表达谱变化,为认识慢性粒细胞白血病(CML)的发病机制、耐药机制提供新的思路,同时也为治疗寻找潜在重要靶标分子。方法:利用GEO数据库下载慢性粒细胞细胞系(K562)基因表达芯片数据,通过差异基因的筛选,趋势分析、GO分析,信号通路分析,最后获得的重要差异表达核心基因,并建立相互作用网络。结果:获得显著表达差异基因1000,通过趋势分析、功能富集分析及信号通路分析提示主要涉及到代谢途径、细胞凋亡、癌症的途径、细胞周期、p53信号通路。相互作用网络分析及同表达相互作用网络分析,得到重要的核心节点基因:AK2、ADSL、PKLR、PKM、SHMT2、ATIC、LDHA、ENO1、CTH、GOT1;YARS、CYP3A5、CTH、GYPA、ALAS2、MTHFD2、BLVRB、GUK1、CTSH、LMO2。结论:利用生物信息学的方法,分析慢性粒细胞白血病细胞基因芯片得到参与不同TKIs处理K562细胞的重要的细胞功能及信号通路主要涉及代谢通路及增殖凋亡信号途径,并且寻找到核心节点基因,为认识K562的耐药机制及治疗靶点提供新的思路。
OBJECTIVE: To investigate the gene expression profiles of K562 cells treated with two tyrosine kinase inhibitors (TKIs), and to provide new ideas for understanding the pathogenesis and mechanism of drug resistance of chronic myeloid leukemia (CML) and to find potential for treatment Important target molecule. Methods: Chromosome array data of chronic granulocytic cell line (K562) were downloaded from GEO database. Core genes were expressed and analyzed through differential gene screening, trend analysis, GO analysis and signal pathway analysis. Finally, we established an interaction network. Results: The differentially expressed genes 1000 were obtained. Through trend analysis, functional enrichment analysis and signal pathway analysis, it was suggested that they involved in metabolic pathways, apoptosis, pathways of cancer, cell cycle and p53 signaling pathway. Interaction network analysis and network analysis of interaction with expression showed important core node genes AK2, ADSL, PKLR, PKM, SHMT2, ATIC, LDHA, ENO1, CTH, GOT1, YARS, CYP3A5, CTH, GYPA, ALAS2, MTHFD2 , BLVRB, GUK1, CTSH, LMO2. Conclusion: Using bioinformatics methods to analyze the important cell functions and signaling pathways involved in the treatment of K562 cells with different TKIs by gene chips of chronic myeloid leukemia cells mainly involve the metabolic pathways and proliferation and apoptosis signaling pathways, and to find the core node genes, K562 for understanding the mechanism of resistance and therapeutic targets provide new ideas.