肺腺癌CASZ1表达临床意义GEO及TCGA数据库资料分析

目的 CASZ1在多种肿瘤中异常表达,并参与肿瘤的发生发展,但其在肺腺癌中的表达及临床意义罕见报道。本研究旨在探讨CASZ1表达水平与肺腺癌临床病理特征和预后的关系。方法通过基因表达谱动态分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库探讨CASZ1在33种肿瘤中的表达情况。通过基因表达综合(Gene Expressi on Omnibus,GEO)数据库及癌症和肿瘤基因图谱(The Cancer Genome Atlas,TCGA)数据库获得CASZ1在肺腺癌中的表达数据及相关病理参数,分析CASZ1表达水平与肺腺癌患者临床病理特征和总生存期(overall survival,OS)的关系,并通过免疫组化验证CASZ1蛋白在肺腺癌中的表达。通过TCGA数据库获得CASZ1在肺腺癌中的甲基化水平,分析肺腺癌中CASZ1表达失调的可能机制。采用基因集富集分析(gene set enrichment analysis,GSEA)预测CASZ1相关的基因通路。结果 GEPIA数据库分析结果显示,与正常组织相比,在11种肿瘤中CASZ1表达水平下调,在2种肿瘤中表达上调。在TCGA及GSE43458、GSE118370和GSE10072既往吸烟、吸烟及从未吸烟数据集中,CASZ1表达水平在肺腺癌组织中均下调,差异有统计学意义,均P<0.001。免疫组化结果提示,CASZ1蛋白在肺腺癌组织中表达也下调,t=5.969,P<0.001。TCGA及GSE68465数据集结果提示,CASZ1基因低表达组预后差于高表达组(χ^2=6.923,P=0.009;χ^2=11.175,P=0.001)。在肺腺癌组织中,CASZ1表达水平与6个甲基化位点(cg01551133、cg08885197、cg20288000、cg14170597、cg22728186和cg20329303)关联(P<0.001),其中cg01551133、cg14170597和cg22728186高甲基化组生存期短于低甲基化水平组(χ^2=11.290,P=0.001;χ^2=12.901,P<0.001;χ^2=7.083,P=0.008)。GSEA结果提示,CASZ1低表达样本富集在G2M检查点(P<0.001,FDR<0.001)、E2F信号通路(P<0.001,FDR<0.001)等基因集。结论肺腺癌中CASZ1表达水平下调,其甲基化水平升高可能是CASZ1失调的潜在机制,CASZ1低表达提示肺腺癌患者的预后差,可作为肺腺癌患者治疗的潜在靶点。

Analysis of the expression and clinical significance of CASZ1 in lung adenocarcinoma based on GEO and TCGA databases

OBJECTIVE CASZ1 is abnormally expressed in a variety of tumors and participates in the development of tumors,but its expression and clinical significance in lung adenocarcinoma are rarely reported.This study is to investigate the expression of CASZ1 and clarify the clinical significance and prognostic value in lung adenocarcinoma.METHODS The expression of CASZ1 in 33 tumors was analysed based on Gene Expression Profiling Interactive Analysis(GEPIA)database.The correlation between CASZ1 and lung adenocarcinoma clinical pathology parameters,as well as the value of its prognosis were studied using the Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO)databases,and immunohistochemical method was used to verify the expression of CASZ1 protein in lung adenocarcinoma.CASZ1 methylation level in lung adenocarcinoma was obtained from TCGA database to analyze the possible mechanism for CASZ1 expression disorder.GSEA predicted the potential signaling pathways.RESULTS The GEPIA database showed that CASZ1 expression was significantly down-regulated in 11 tumors,and increased in 2 tumors.Based on TCGA,GSE43458,GSE118370,GSE10072(previous smoking,smoking and never smoking)databases,the expression level of CASZ1 was significantly down-regulated in lung adenocarcinoma tissues,all P<0.001.Immunohistochemical results showed that the expression of CASZ1 protein in lung adenocarcinoma was also down-regulated(t=5.969,P<0.001).The results of the TCGA and GSE68465 datasets showed that LUAD patients with low expression of CASZ1 gene had a worse prognosis than patients with high expression(χ^2=6.923,P=0.009;χ^2=11.175,P=0.001).The CASZ1 expression in lung adenocarcinoma was significantly correlated with 6 methylation sites(cg01551133,cg08885197,cg20288000,cg14170597,cg22728186,cg20329303,P<0.001),and the cg01551133,cg14170597,and cg22728186 hypermethylation groups had shorter survival than the hypomethylation group(χ^2=11.290,P=0.001;χ^2=12.901,P<0.001;χ^2=7.083,P=0.008).GSEA showed that lowCASZ1 expression was enriched in the G2 M checkpoint(P<0.001,FDR<0.001),E2 Fsignaling pathway(P<0.001,FDR<0.001)and other signaling pathways.CONCLUSIONS The expression of CASZ1 is down-regulated in lung adenocarcinoma.The methylation may be a potential mechanism of CASZ1 dysregulation.The low expression of CASZ1 suggests poor prognosis and may serve as a therapy target in lung adenocarcinoma.