CDCA8和INCENP mRNA在肝细胞癌组织中的表达及其临床意义  

Expressions of CDCA8 and INCENP mRNAs in hepatocellular carcinoma and their clinical significance

作　　者：张路遥[1] 黄辉星[1] 曹立环[1] 余龙[1] ZHANG Luyao HUANG Huixing CAO Lihuan YU Long(National Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, Chin)

机构地区：[1]复旦大学生命科学学院遗传工程国家重点实验室,上海200438

出　　处：《中国肿瘤生物治疗杂志》2017年第2期158-167,共10页Chinese Journal of Cancer Biotherapy

基　　金：国家科技重大专项资助项目(No.2013ZX10002010)~~

摘　　要：目的:探讨CDCA8和INCENP mRNA在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法:使用Illumina Nextbio芯片数据库分析原发性HCC组织和相应癌旁组织中CDCA8和INCENP mRNA表达情况,在癌症基因组图谱(The Cancer Genome Atlas,TCGA)肝癌数据库中使用RNA-Seq mRNA表达数据进行验证,并结合TCGA临床数据分析CDCA8和INCENP mRNA表达水平与HCC患者临床病理特征及预后的关系,使用基因集富集软件分析目的基因高表达的相关通路。结果:CDCA8和INCENP mRNA在HCC组织中表达水平显著上调(P<0.01)。CDCA8 mRNA表达水平与HCC的组织学分级、瘤体大小、肿瘤复发、美国东部肿瘤协作组织(ECOG)评级、血清AFP水平、肿瘤基因拷贝数变异显著相关(P<0.05);INCENP mRNA表达水平与HCC的组织学分级、肿瘤复发、ECOG评级、血清AFP水平、肿瘤基因突变总数和肿瘤基因拷贝数变异显著相关(P<0.05)。CDCA8高表达组患者的OS及TFS显著低于CDCA8低表达组患者(P<0.01);INCENP高表达组患者的OS显著低于INCENP低表达组患者(P<0.05),而TFS无显著差异(P>0.05)。多因素分析显示,CDCA8 mRNA水平是预测HCC患者不良预后的独立因素(P<0.01)。基因集富集分析表明,CDCA8和INCENP可能在细胞周期之外的其他生物学信号通路中发挥一定作用。结论:CDCA8和INCENP mRNA在HCC组织中呈现显著高表达。CDCA8可能成为HCC预后的独立风险因素和新的治疗靶点。Objective：To explore expressions of CDCA8 and INCENP mRNAs in hepatocellular carcinoma （HCC） and their clinical significance. Methods：Illumina Nextbio microarray database was used to analyze expressions of CDCA8 and INCENP mRNAs in primary HCC and paired adjacent liver tissues. The results were verified by the RNA-Seq mRNA expression data in liver cancer database of The Cancer Genome Atlas （TCGA）. Then correlations of the CDCA8 and INCENPmRNAs expressions with clinicopathological features and prognosis of the patients with HCC were analyzed combining with clinical data of TCGA. Gene sets enrichment analysis （GSEA） software was used to analyze the related pathways for high expressions of the target genes. Results： The expression levels of CDCA8 and INCENP mRNAs were significantly upregulated in HCC tissues （P〈0.01）. The expression level of CDCA8 mRNA was significantly correlated with histological grade, clinical stage, tumor diameter, recurrence, Eastern Cooperative Oncology Group of the United States （ECOG） grade, serum alpha fetal protein （AFP） concentration and copy number alteration （CNA） of the patients with HCC （P〈0.05）. The expression level of INCENP mRNA was evidently correlated with histological grade, recurrence, ECOG grade, serum AFP concentration, mutation counts and CNA of the patients with HCC （P〈0.05）. Overall survival （OS） and tumor free survival （TFS） of the patients with higher expression level of CDCA8 mRNA were significantly shorter than those of the patients with lower expression level of CDCA8 mRNA （P〈0.01）. OS of the patients with higher expression level of INCENP mRNA was significantly shorter than that of the patients with lower expression level of INCENT mRNA （P〈0.05）. However, there was no significant difference of TFS between the patients with higher expression level and lower expression level of INCENT mRNA. Multivariate analysis showed that the expression level of CDCA8 mRNA was an independent factor for poor

关 键 词：肝细胞癌 肿瘤基因组图谱 细胞分裂周期相关蛋白8 内着丝粒结合蛋白 预后 

分 类 号：R735.7[医药卫生—肿瘤] R730.2[医药卫生—临床医学]