MAPK13基因表达在非小细胞肺癌临床预后中的作用
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摘要
目的:使用生物信息学来确定与非小细胞肺癌(NSCLC)发展相关的潜在关键基因及其涉及的信号通路,探讨所得关键基因表达水平在NSCLC临床预后中的作用。方法:从GEO数据库中获取NSCLC基因芯片数据并使用R语言分析筛选差异表达基因;通过DAVID数据库进行差异基因的KEGG通路富集分析,通过STRING数据库及Cytoscape软件构建差异表达基因的蛋白—蛋白相互作用网络(PPI)并筛选关键基因。通过Kaplan Meier plotter在线数据库对NSCLC患者进行生存分析。结果:共筛选出61个差异表达基因;差异表达基因主要富集在癌症相关的信号通路;PPI网络分析表明,丝裂原活化蛋白激酶13(MAPK13)基因是重要的关键基因;Kaplan Meier plotter分析显示,MAPK13基因表达水平与NSCLC患者预后明显相关,MAPK13基因表达水平越高生存率越高(HR=0.8,95%CI:0.70～0.91,P<0.05)。结论:MAPK13基因在NSCLC的发生发展中可能起着重要作用,是潜在的预后分子标志物。
Objective:To identify the underlying key genes and involved signal pathways associated with the development of non-small cell lung cancer(NSCLC)by bioinformatics analysis,and explore the effect of target gene expression in the prognosis of NSCLC.Methods:Microarray dataset of NSCLC was obtained from the Gene Expression Omnibus(GEO)database,and differentially expressed genes were screened by using R software.Pathway enrichment analysis were performed based on Kyoto Encyclopedia of Genes and Genomes(KEGG) database.A protein-protein interaction(PPI)network was constructed through STRING and Cytoscape to screen key genes.The survival analysis was performed by Kaplan Meier plotter online tool.Results:A total of 61 differentially expressed genes were identified.The differentially expressed genes mainly involved in cancer related signaling pathway.The PPI network analysis suggested that mitogen-activated protein kinase(MAPK)13 gene was a key gene.Kaplan Meier plotter analysis showed that the MAPK13 expression level was obviously correlated with the prognosis of NSCLC.The higher the MAPK13 level,the better the prognosis(HR=0.8,95%CI:0.70-0.91,P<0.05).Conclusion:MAPK13 might play an important role in the occurrence and development of NSCLC and it could be a potential prognostic molecular marker.
Objective:To identify the underlying key genes and involved signal pathways associated with the development of non-small cell lung cancer(NSCLC)by bioinformatics analysis,and explore the effect of target gene expression in the prognosis of NSCLC.Methods:Microarray dataset of NSCLC was obtained from the Gene Expression Omnibus(GEO)database,and differentially expressed genes were screened by using R software.Pathway enrichment analysis were performed based on Kyoto Encyclopedia of Genes and Genomes(KEGG) database.A protein-protein interaction(PPI)network was constructed through STRING and Cytoscape to screen key genes.The survival analysis was performed by Kaplan Meier plotter online tool.Results:A total of 61 differentially expressed genes were identified.The differentially expressed genes mainly involved in cancer related signaling pathway.The PPI network analysis suggested that mitogen-activated protein kinase(MAPK)13 gene was a key gene.Kaplan Meier plotter analysis showed that the MAPK13 expression level was obviously correlated with the prognosis of NSCLC.The higher the MAPK13 level,the better the prognosis(HR=0.8,95%CI:0.70-0.91,P<0.05).Conclusion:MAPK13 might play an important role in the occurrence and development of NSCLC and it could be a potential prognostic molecular marker.
引文
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[6]YANG W,XIA Y,HAWKE D,et al.PKM2phosphorylates histone H3and promotes gene transcription and tumorigenesis[J].Cell,2012,150(4):685-696.
[7]CHEN G M,ZHENG A J,CAI J,et al.microRNA-145-3p inhibits non-small cell lung cancer cell migration and invasion by targeting PDK1via the mTOR signaling pathway[J].Journal of Cellular Biochemistry,2018,119(1):885-895.
[8]PURI T.Targeted therapy in nonsmall cell lung cancer[J].Indian Journal of Cancer,2017,54(1):83-88.
[9]TIAN H,YIN L,DING K,et al.Raf1is a prognostic factor for progression in patients with nonsmall cell lung cancer after radiotherapy[J].Oncology Reports,2018,39(4):1966-1974.
[10]TAN F L,OOI A,HUANG D,et al.p38delta/MAPK13as a diagnostic marker for cholangiocarcinoma and its involvement in cell motility and invasion[J].International Journal of Cancer,2010,126(10):2353-2361.
[11]YASUDA K,YOSHIHIKO H,KURODA T,et al.MAPK13is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation[J].Biochemical&Biophysical Research Communications,2016,472(4):643-647.
[12]YASUDA K,HIROHASHI Y,KURODA T,et al.MAPK13is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation[J].Biochemical&Biophysical Research Communications,2016,472(4):643-647.
[2]张小强,杜延玲.肺癌患者预后评估相关指标的研究进展[J].临床误诊误治,2017,30(12):105-109.
[3]KANEHISA M,GOTO S.KEGG:kyoto encyclopedia of genes and genomes[J].Nucleic Acids Research,2000,28(1):27-30.
[4]PRIFTI E,ZUCKER J D,CLEMENT K,et al.Interactional and functional centrality in transcriptional co-expression networks[J].Bioinformatics,2010,26(24):3083-3089.
[5]HAN Z,WANG T,SHUAI H,et al.Low-expression of TMEM100is associated with poor prognosis in nonsmall-cell lung cancer[J].American Journal of Translational Research,2017,9(5):2567-2578.
[6]YANG W,XIA Y,HAWKE D,et al.PKM2phosphorylates histone H3and promotes gene transcription and tumorigenesis[J].Cell,2012,150(4):685-696.
[7]CHEN G M,ZHENG A J,CAI J,et al.microRNA-145-3p inhibits non-small cell lung cancer cell migration and invasion by targeting PDK1via the mTOR signaling pathway[J].Journal of Cellular Biochemistry,2018,119(1):885-895.
[8]PURI T.Targeted therapy in nonsmall cell lung cancer[J].Indian Journal of Cancer,2017,54(1):83-88.
[9]TIAN H,YIN L,DING K,et al.Raf1is a prognostic factor for progression in patients with nonsmall cell lung cancer after radiotherapy[J].Oncology Reports,2018,39(4):1966-1974.
[10]TAN F L,OOI A,HUANG D,et al.p38delta/MAPK13as a diagnostic marker for cholangiocarcinoma and its involvement in cell motility and invasion[J].International Journal of Cancer,2010,126(10):2353-2361.
[11]YASUDA K,YOSHIHIKO H,KURODA T,et al.MAPK13is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation[J].Biochemical&Biophysical Research Communications,2016,472(4):643-647.
[12]YASUDA K,HIROHASHI Y,KURODA T,et al.MAPK13is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation[J].Biochemical&Biophysical Research Communications,2016,472(4):643-647.