基于数据库挖掘分析CKMT1A在非小细胞肺癌化疗耐药性中的作用

Analysis of the Role of CKMT1A on Non-small Cell Lung Cancer Chemotherapy Resistant Based on Data Mining

目的探讨线粒体肌酸激酶1A(creatine kinase mitochondrial 1A,CKMT1A)在非小细胞肺癌(non-small cell lung cancer,NSCLC)化疗耐药性中的作用。方法通过HPA、GEPIA、GEO等数据库或在线分析工具分析CKMT1A在NSCLC及顺铂耐药性NSCLC细胞系的表达,运用非配对t检验分析组间差异;通过STRING结合DAVID 6.8分析CKMT1A互作基因的通路富集,运用Fisher Exact Test计算富集P值;microRNA.org结合Targetscan进行miRNA-mRNA互作分析进一步证明CKMT1A在NSCLC化疗耐药性中的作用;运用COREMINE工具进行文本挖掘分析显著富集的通路与NSCLC化疗耐药性的关系,以及microRNA与NSCLC化疗耐药性的关系;通过Kaplan Meier-plotter运用log-rank检验分析CKMT1A表达量、microRNA表达量与NSCLC患者总生存率(overall survival,OS)的相关性,以及CKMT1A表达量与NSCLC化疗患者OS的相关性。结果CKMT1A在NSCLC患者及顺铂耐药性的NSCLC细胞系中的表达量显著升高(P=0.000),而且与患者的OS显著相关(P<0.05);代谢途径,尤其是精氨酸和脯氨酸代谢途径在CKMT1A互作基因中具有显著性富集(P<0.05),而且与NSCLC化疗耐药性密切相关;hsa-miR-103和hsa-miR-107靶向于CKMT1A,而且与NSCLC患者OS和化疗耐药性相关。结论高表达CKMT1A影响NSCLC的预后及化疗耐药性,而且有可能通过精氨酸和脯氨酸代谢途径或者microRNA转录后调控介导NSCLC化疗耐药性。

OBJECTIVE To explore the role of creatine kinase mitochondrial 1A(CKMT1A)on non-small cell lung cancer(NSCLC)chemotherapy resistant.METHODS HPA,GEPIA,GEO databases or online tools were used to explore the expression of CKMT1A on NSCLC or cisplatin resistant NSCLC cell line,the difference between two groups was evaluated by unpaired t test.Pathway enrichment analysis of CKMT1A interacted genes was conducted by STRING and DAVID 6.8,enriched P value was evaluated by Fisher Exact Test.miRNA-mRNA interaction analysis was conducted by microRNA.org and Targetscan to further prove the role of CKMT1A on NSCLC chemotherapy resistant.The relation of CKMT1A expression or microRNA expression and NSCLC overall survival(OS)were conducted by Kaplan Meier-plotter using log-rank test.COREMINE was used to analyze the relation of enriched pathways and NSCLC chemotherapy resistant and the relation of microRNA and NSCLC chemotherapy resistant.RESULTS CKMT1A were over expressed in NSCLC and cisplatin resistant NSCLC cell line(P=0.000).High expression of CKMT1A was significantly associated with lower OS in NSCLC(P<0.05).Metabolic pathways,especially arginine and proline metabolism pathway were enriched among genes interacted with CKMT1A(P<0.05),which was closely associated with NSCLC chemotherapy resistant.hsa-miR-103 and hsa-miR-107 were target to CKMT1A,and also associated with NSCLC OS and chemotherapy resistant.CONCLUSION CKMT1A over-expression affect clinical prognosis and chemotherapy resistant in NSCLC,and possibly by arginine and proline metabolism pathway or microRNA post-transcriptional regulation.