基于生物信息学分析细胞分裂周期蛋白20在肝癌中的表达及预后意义

The expression and prognostic significance of cell division cycle 20 in liver cancer based on bioinformatics

目的探讨肝癌组织中细胞分裂周期蛋白20(CDC 20)的表达及临床预后价值。方法从癌症基因组图谱(TCGA)数据库下载肝癌转录组和临床数据,使用R和Perl软件进行数据分析整理,采用Wilcoxon秩和检验分析基因CDC20的差异表达以及与临床病理特征相关性,Kaplan-Meier和Cox回归分析肝癌患者预后影响因素。基因集富集分析(GSEA)方法分析基因CDC20的调控网络,探究潜在机制。计数资料比较采用χ^(2)检验。结果基因CDC20在肝癌组织中的表达量显著高于正常组织[5.25(2.19,13.59)比0.21 (0.14,0.37),Z=-11.0,P<0.01],其高表达与患者的不良预后显著相关(P<0.01);CDC20表达量与肿瘤的组织学分级(G1/G2/G3/G4分别为2.43(0.89,9.39)比4.51(1.53,10.55)比8.79(3.85,19.08)比15.12(4.42,25.10),Z=-2.69,P<0.01)、临床分期(Ⅰ+Ⅱ/Ⅲ+Ⅳ为4.70(2.16,10.57)比8.54(3.04,19.97),Z=-2.78,P<0.01)以及TNM分期中的T分期(T1/T2/T3/T4为3.95(1.57,9.13)比7.77(3.05,16.05)比8.54(1.86,20.79)比12.36(4.34,27.70),Z=-3.98,P<0.01)成正相关;GSEA分析提示,CDC20参与了细胞周期、DNA复制、肿瘤、泛素介导蛋白水解作用、Notch等信号通路;基因CDC20可作为评估患者预后的独立风险因子,可用于肝癌的诊断和预后判断。结论 CDC20在肝癌组织中高表达,与患者的不良预后密切相关,可作为肝癌预后的独立危险因子,其可能通过p21蛋白泛素化降解和Notch信号通路在肝癌中发挥促癌作用。

Objective To analyze the expression of cell division Cycle 20(CDC 20)in liver cancer and its clinical prognostic value.Methods The transcriptomic and clinical data of liver cancer were downloaded from the cancer Genome Atlas(TCGA)database,and analyzed by R and Perl software.Wilcoxon rank sum test was used to analyze the differential expression of CDC20 and correlation between CDC20 and clinicopathological features,and Kaplan-Meier and Cox regression were used to analyze the prognostic factors.Gene Set Enrichment Analysis(GSEA)was used to analyze the regulatory network of Gene CDC20 to explore the potential mechanism.P<0.05 was considered statistically significant.Results The expression of CDC20 gene in liver cancer tissue was significantly higher than that in normal tissue[5.25(2.19,13.59)/0.21(0.14,0.37),Z=-11.0,P<0.01],and its high expression was significantly correlated with the poor prognosis of patients(Kaplan-Meier and log-rank test,P<0.01).The expression level of CDC20 was positively correlated with histological grade[G1/G2/G3,G4 were 2.43(0.89,9.39)/4.51(1.53,10.55)/8.79(3.85,19.08),15.12(4.42,25.10),Z=-2.69,P<0.01]and clinical stage of tumor[Ⅰ+Ⅱ/Ⅲ+Ⅳwere 4.70(2.16,10.57)/8.54(3.04,19.97),Z=-2.78,P<0.01]and T stage[T1/T2/T3/T4 were 3.95(1.57,9.13)/7.77(3.05,16.05)/8.54(1.86,20.79)/12.36(4.34,27.70),Z=-3.98,P<0.01]in TNM stage.GSEA analysis suggested that CDC20 was involved in cell cycle,DNA replication,tumor,ubiquitin-mediated proteolysis,Notch signaling pathway and other signaling pathways.CDC20 gene can be used as an independent risk factor to evaluate the prognosis of patients,and can be used in the diagnosis and prognosis of liver cancer.Conclusion CDC20 is highly expressed in liver cancer tissue,which is closely related to poor prognosis of patients,and can be used as an independent risk factor for prognosis of liver cancer.CDC20 may play an important role in the development of liver cancer through the ubiquitinization degradation of p21 protein and Notch signaling pathway.