基于TCGA数据库的肺腺癌组织中CDT1表达及相关信号通路分析

Analysis of CDT1 expression and related signal pathways in lung adenocarcinoma based on TCGA database

目的基于症基因组图谱(TCGA)数据库,观察染色质许可和DNA复制因子1(CDT1)在肺腺癌患者癌组织中的表达变化,分析癌组织中CDT1与患者临床病理特征、预后的相关性,并预测CDT1在肺腺癌中参与调节的信号通路。方法从TCGA数据库中下载肺腺癌组织中CDT1基因表达谱及肺腺癌患者的临床病理信息,使用R3.6.1软件提取肺腺癌组织(肺腺癌组)及正常肺组织(正常对照组)CDT1的表达量数据,利用Mann-Whitney U检验比较两组间的表达差异。以CDT1表达水平的中位值(4.409)为界限将肺腺癌患者分为CDT1高表达组和CDT1低表达组,利用单因素及多因素COX回归分析癌组织中CDT1表达与患者临床病理特征的关系。利用R3.6.1软件"survival"包分析CDT1高、低表达组总体生存率(OS)的差异,并通过GEPIA、Kaplan Meier-plotter、UALCAN等在线工具对结果进行验证。利用基因集富集分析(GSEA)预测CDT1在肺腺癌中参与的分子通路。结果肺腺癌组CDT1的表达水平高于正常对照组(P<0.001)。肺腺癌组织中CDT1的表达水平与患者年龄(P=0.019)、Stage分期(P=0.007)及远处转移(P=0.042)等相关。Stage分期(HR=1.97,95%CI:1.22~3.17,P=0.005)和CDT1表达(HR=1.43,95%CI:1.14~1.79,P=0.002)可以作为肺腺癌的独立预后因素。CDT1高表达组生存率低于CDT1低表达组(P=0.029)。CDT1主要参与细胞周期、嘌呤与嘧啶代谢、核苷酸切除修复以及p53信号通路等。结论CDT1在肺腺癌患者中高表达,与肺腺癌患者的Stage分期及远处转移等相关,可作为导致肺腺癌不良预后的独立危险因子,并通过参与多种信号通路促进肺腺癌的发生发展。

Objective To investigate the expression changes of chromatin licensing and DNA replication factor 1(CDT1)in patients with lung adenocarcinoma and its correlation with clinicopathological characteristics and prognosis,and to predict the signal pathway that CDT1 participates in the regulation of lung adenocarcinoma.Methods CDT1 gene expression profile and clinicopathological information of patients in lung adenocarcinoma were downloaded from The Cancer Genome Atlas(TCGA)database.The expression level of CDT1 in the lung adenocarcinoma group and the normal control group was extracted by R 3.6.1 software.The Mann-Whitney U test was used to analyze the expression difference between two groups.Lung adenocarcinoma patients were divided into the high expression group and low expression group with the median value of CDT1 expression level(CDT1 Median=4.409)as the limit.Chi-square test was conducted to analyze the correlation between CDT1 expression and clinicopathological features.Univariate and multivariate COX risk regression models were exerted to analyze the prognostic indicators of lung adenocarcinoma.We applied the"survival"package of the R3.6.1 software for survival analysis,and meanwhile,GEPIA,Kaplan-Meier-plotter,UALCAN and other online tools were utilized to verify the gene expression and prognostic effect.Gene Set Enrichment Analysis(GSEA)was used to predict the molecular pathways involved in CDT1 in the lung adenocarcinoma.Results The expression of CDT1 in the lung adenocarcinoma group was higher than that in the normal control group(P<0.001).The expression level of CDT1 in the lung adenocarcinoma tissues was related to age(P=0.019),Stage(P=0.007)and distant metastasis(P=0.042).Stage(HR=1.97,95%CI:1.22-3.17,P=0.005)and CDT1(HR=1.43,95%CI:1.14-1.79,P=0.002)were independent risk factors for prognosis of lung adenocarcinoma patients.The overall survival(OS)of CDT1 in the high expression group was lower than that of the low expression group(P=0.029).CDT1 was mainly involved in the cell cycle,purine and pyrimidine metabolism,nucleotide resection and repair and p53 signaling pathway.Conclusion CDT1 was highly expressed in patients with lung adenocarcinoma and was related to the Stage and distant metastasis of lung adenocarcinoma;CDT1 was an independent risk factor for poor prognosis of lung adenocarcinoma,and it could promote the occurrence and development of lung adenocarcinoma by participating in multiple signal pathways.