基于生物信息学分析CCNB1在肺腺癌组织中的表达及其与预后的关系

Expression of CCNB1 in lung adenocarcinoma and its relationship with prognosi a bioinformatic analysis

目的评估细胞周期蛋白B1(cyclin B1,CCNB1)基因表达与肺腺癌预后的相关性。方法使用Oncomine、STRING、人类蛋白质图谱、癌症基因组图谱等数据库以及Kaplan-Meier、Cox回归分析、受试者操作特征(receiver operating characteristic,ROC)曲线、Spearman相关分析等方法来验证CCNB1对肺腺癌患者的影响。结果CCNB1在肺腺癌组织中高表达,且与肺腺癌患者的T分期(P=0.001)、N分期(P<0.001)、病理分期(P<0.001)以及性别(P=0.008)等临床特征相关。单因素Cox回归分析结果显示CCNB1的表达、T分期、N分期、M分期、病理分期是影响肺腺癌患者总生存率的因素(P<0.05),多因素Cox回归分析显示CCNB1的表达、T分期是肺腺癌患者总生存率的独立危险因素(P<0.05)。Kaplan-Meier分析得出,CCNB1高表达与较短的总生存期[风险比(hazard ratio,HR)=1.60,95%置信区间(confidence interval,CI)(1.20,2.14),P=0.002]、疾病特异性生存期[HR=1.68,95%CI(1.16,2.44),P=0.006]、无进展间期[HR=1.42,95%CI(1.09,1.85),P=0.009]相关。ROC曲线表明CCNB1可能是肺腺癌的诊断分子[曲线下面积=0.980,95%CI(0.967,0.993)]。Spearman相关分析显示,CCNB1的表达与T辅助细胞2(r_(s)=0.805,P<0.001)及T辅助细胞(r_(s)=0.103,P=0.017)的浸润呈正相关,与自然杀伤细胞(r_(s)=-0.195,P<0.001)、巨噬细胞(r_(s)=-0.134,P=0.002)、T细胞(r_(s)=-0.092,P=0.033)的浸润呈负相关。结论与正常组织相比,CCNB1在肺腺癌中高表达,与不良预后具有相关性,可能为肺腺癌患者提供潜在的治疗靶点。

Objective To evaluate the correlation between cyclin B1(CCNBI)gene expression and the prognosis of lung adenocarcinoma.Methods Oncomine,STRING,Human Protein Atlas,The Cancer Genome Atlas and other databases as well as Kaplan-Meier method,Cox regression,receiver operating characteristic(ROC)curve and Spearman correlation analysis were used to verify the effect of CCNBl on patients with lung adenocarcinoma.Results CCNB1 was highly expressed in lung adenocarcinoma,and the high expression was correlated with T stage(P=0.001),N stage(P<0.001),pathological stage(P<0.001)and gender(P=0.008).Univariate Cox regression analysis showed that the expression of CCNBi,T stage,N stage,M stage and pathological stage were the factor_(s) affecting the overall survival rate of patients with lung adenocarcinoma(P<0.05);multivariate Cox regression analysis showed that the expression of CCNB1 and T stage were independent risk factor_(s) for overall survival of patients with lung adenocarcinoma(P<0.05).Kaplan-Meier analysis showed that high expression of CCNB1 was associated with shorter overall survival[hazard ratio(HR)=1.60,95%confidence interval(CI)(1.20,2.14),P=0.002],disease-specific survival[HR=1.68,95%CI(1.16,2.44),P=0.006]and progression-free interval[HR=1.42,95%CI(1.09,1.85),P=0.009].The ROC curve showed that CCNB1 might be a potential diagnostic molecule for lung adenocarcinoma[area under the curve=0.980,95%CI(0.967,0.993)].Spearman correlation analysis showed that CCNB1 expression was positively correlated with the infiltration of T helper cells 2(r_(s)=0.805,P<0.001)and T helper cells(r_(s)=0.103,P=0.017),and negatively correlated with the infiltration of natural killer cells(r_(s)=-0.195,P<0.001),macrophages(r_(s)=-0.134,P=0.002),and T cells(r=-0.092,P=0.033).Conclusion CCNB1 is highly expressed in lung adenocarcinoma compared with normal tissues,which is related to poor prognosis and may provide a potential therapeutic target for patients with lung adenocarcinoma.