基于生物信息学途径预测MELK基因在肺腺癌及肺鳞癌中的功能机制及临床意义

Prediction of Functional Mechanism and Clinical Significance of MELK in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma Based on Bioinformatics Analysis

【目的】通过生物信息学方法,预测肺腺癌及肺鳞癌中高表达的母体胚胎亮氨酸拉链激酶(MELK)在疾病发生发展中的功能机制及临床意义。【方法】从基因表达数据(GEO)获取芯片数据集GSE7670,结合肿瘤基因组图谱(TCGA)肺腺癌及肺鳞癌数据库进行差异分析,筛选差异激酶(P<0.05)。对这些激酶进行GO生物学功能富集分析及KEGG信号通路分析。通过String数据库绘制蛋白相互作用网络,并利用Cytoscape的MCODE插件找到关键节点蛋白,挑选出MELK激酶。通过Oncomine数据库分析MELK表达,从TCGA数据库获取临床信息,分析MELK表达与肺腺癌及肺鳞癌临床病理特征及预后的关系。采用GeneMANIA预测MELK功能,进而用GEPIA2验证相关共表达基因。【结果】共筛选出159个与细胞增殖、凋亡及各信号通路密切相关的差异激酶。蛋白质相互作用网络分析发现21个关键基因。MELK在男性、年龄较小、高分期的肺腺癌及肺鳞癌中表达较高。在肺腺癌中,MELK高表达与较短的总生存期(OS)及无进展生存期(PFS)显著相关,而在肺鳞癌中则无显著差异。MELK可能参与G2/M期转化,且在肺腺癌及肺鳞癌中均与增殖相关基因MKI67、PCNA、CCNB1、MCM2和TOP2A共表达。【结论】MELK在肺腺癌及肺鳞癌中高表达,可能通过促进细胞有丝分裂及细胞周期G2/M期转化参与肺腺癌的发生发展,有望成为肺腺癌新的生物标记物。

【Objective】To predict the functional mechanism and clinical significance of highly expressed maternal embryonic leucine zipper kinase(MELK)in lung adenocarcinoma and lung squamous cell carcinoma by bioinformatics.【Methods】The chip data set GSE7670 was obtained from the Gene Expression Omnibus(GEO)database and combined with the TCGA lung adenocarcinoma(LUAD)and lung squamous cell carcinoma(LUSC)database for differential analy⁃sis,and to screen out differential kinases(P<0.05).GO biological function enrichment and KEGG pathway analysis of these kinases were performed.Based on String,a protein interaction network was obtained.MCODE plug-in of Cytoscape was applied to find key node proteins and then MELK kinase protein was picked out.MELK expression was analyzed through Oncomine database.Clinical information from TCGA database was obtained,and the relationship between MELK expression and clinicopathological characteristics,prognosis of LUAD and LUSC was analyzed.GeneMANIA was used to predict the function of MELK,and then to verify related co-expressed genes with GEPIA2.【Results】A total of 159 differential kinases were screened out,which were closely related to cell proliferation,apoptosis and various signal pathways.Twenty-one important genes were identified by analyzing protein interaction networks. MELK level was higher in male,young or advanced clinical stage lung adenocarcinoma and lung squamous cell carcinoma. The patients with high MELKlevels had a shorter progression-free survival(PFS)and overall survival(OS)in LUAD,but there was no significant dif⁃ference in LUSC. MELK was involved in G2/M transition possibly and was co-expressed with proliferation-related genes(MKI67,PCNA,CCNB1,MCM2,and TOP2A)in LUAD and LUSC.【Conclusions】MELK is highly expressed in LUADand LUSC. MELK may be involved in the occurrence and development of LUAD by promoting cell mitosis and G2/Mtransition. MELK could be a new biomarker for LUAD.