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 prognosis of the patients with HCC (P<0.01). Analization of GSEA indicated that CDCA8 and INCENT may play cerntain roles in other biological pathways except cell cycle-related pathways. Conclusion: Expressions of CDCA8 and INCENP mRNAs appeared significant high levels in HCC tissues. CDCA8could be as an independent risk factor for prognosis of HCC and a potential novel target for therapy of the patients with HCC.

国家科技重大专项资助项目（No. 2013ZX10002010）