基于TCGA数据库数据NME基因家族生物学功能、在肝癌诊断和预后预测中的应用分析

Analysis of biological function of NME gene family based on TCGA database and its application in diagnosis and prognosis of liver cancer

目的基于TCGA数据库数据分析肿瘤转移相关(NME)基因家族(NME 1、2、3、4、5、6、7)生物学功能、相关信号通路,并探讨NME基因家族成员对肝癌的诊断、预测预后效能及其与肝癌患者预后的关系。方法从TCGA数据库获取NME基因家族在肝癌组织和癌旁组织中的表达水平和肝癌患者临床病理资料。对NME基因进行基因本体论(GO)及KEGG代谢通路分析。比较肝癌组织与癌旁组织中NME基因的表达。应用ROC评价NME基因对肝癌的诊断效能。采用单因素生存分析、Log-rank检验和多因素COX生存分析法分析NME基因家族与肝癌患者预后的关系。结果NME基因主要参与调节核苷二磷酸激酶活性、细胞凋亡、发育等生物学过程,主要涉及新陈代谢、抗生素合成、嘌呤和嘧啶代谢途径等相关通路。肝癌组织中NME1、NME2、NME3、NME6、NME7水平均高于癌旁组织(t分别为8.927、7.044、5.267、8.370、4.349,P均<0.0001),肝癌组织中NME5水平低于癌旁组织(t=4.306,P<0.0001),肝癌组织及癌旁组织中NME4水平比较,t=1.403,P=0.1613。除NME4外,其他NME基因家族对肝癌的诊断效能良好,曲线下面积(AUC)分别为0.8872、0.8262、0.7459、0.7457、0.8715、0.7255。吸烟等危险因素、TMN分期、肿瘤浸润情况和是否治疗新发肿瘤影响肝癌患者的生存时间,P均<0.01;NME6和NME7与肝癌患者的预后相关,P均<0.05;NME5、NME6、NME7低表达组肝癌患者的总生存时间高于高表达组(P均<0.05)。结论NME基因家族主要参与调节核苷二磷酸激酶活性、细胞凋亡和细胞发育等生物过程,影响细胞新陈代谢和嘌呤、嘧啶代谢等相关通路。除NME4外,其他NME基因家族对肝癌的诊断效能良好。NME5、NME6、NME7基因水平与肝癌患者的预后相关,可预测预后。

Objective To analyze the biological function and related signaling pathways of tumor metastasis-related(NME)gene family(NME1,2,3,4,5,6,and 7)and to discuss the diagnostic efficacy of NME gene family members for liver cancer and prognosis of liver cancer patients as well as the relation with the prognosis.Methods The clinicopathologic data of the NME gene family in liver cancer tissues and adjacent tissues and clinical information of liver cancer patients were obtained from TCGA database,and GO enrichment analysis and KEGG pathway analysis were conducted for NME genes.The expression of NME genes in the liver cancer tissues and adjacent tissues was analyzed,and ROC curve was used to evaluate the diagnostic efficacy of NME genes in liver cancer.Univariate survival analysis,Log-rank test and multivariate COX survival analysis were used to predict the relationship between NME gene family and prognosis of liver cancer patients.Results The results of GO enrichment analysis indicated that NME gene family were mainly enriched in adjusting nucleoside diphosphate kinase activity,apoptosis,cell growth and other biological processes.The result of KEGG signaling pathway analysis showed that NME gene family were mainly involved in metabolism,antibiotic synthesis,purine and pyrimidine metabolism pathways.The expression levels of NME1,NME2,NME3,NME6,and NME7 in the liver cancer tissues were higher than those in the adjacent tissues(t=8.927,7.034,5.267,8.370,4.349,all P<0.0001).The NME5 expression level in the liver cancer tissues was lower than that in the adjacent tissues(t=4.306,P<0.0001);there was no significant difference in expression of NME4 between the liver cancer tissues and adjacent tissues(t=1.403,P=0.1613).Except for NME4,other NME gene families had good diagnostic efficiency for liver cancer,and the area under the curve(AUC)were 0.8872,0.8262,0.7459,0.7457,0.8715,and 0.7255,respectively.Smoking and other risk factors,TMN staging,tumor invasion and treatment of new tumors affected the survival time of liver cancer patients(all P<0.01);NME6 and NME7 were related to the prognosis of liver cancer patients(both P<0.05);the overall survival time of patients with low expression of NME5,NME6,and NME7 was higher than that of patients with high expression(P<0.05).Conclusions The NME gene family mainly participate in adjusting nucleoside diphosphate kinase activity,apoptosis and cell growth,and affecting cell metabolism and purine and pyrimidine metabolism pathway.Except for NME4,other NME gene family members have good diagnostic efficiency for liver cancer.The levels of NME5,NME6 and NME7 genes are related to the prognosis of liver cancer patients and can predict the prognosis.