CDCA8对肝细胞癌患者预后的影响

Effect of CDCA8 on the prognosis of patients with hepatocellular carcinoma

摘要:

目的 肝细胞癌预后相关的分子标志物对提高患者生存质量和改善疗效至关重要，本研究旨在探究细胞分裂周期相关基因8（cell division cycle associated 8，CDCA8）对肝细胞癌预后的影响及潜在分子机制。方法 432例肝细胞癌样本的转录组数据及对应患者的临床信息下载自肿瘤基因表达图谱（The Cancer Genome Atlas，TCGA）数据库。分析肿瘤组织和正常组织中CDCA8 mRNA差异；根据CDCA8 mRNA中位数将肝细胞癌患者分为高表达组和低表达组，绘制生存曲线。采用Kruskal检验分析CDCA8与肿瘤分期、分级和T分期的相关性。采用单因素和多因素Cox回归分析探究CDCA8能否作为肝细胞癌患者的独立预后因子。采用基因集富集分析（gene set enrichment analysis，GSEA）探究CDCA8在肝细胞癌中的潜在作用机制。结果 CDCA8在肿瘤组织中的mRNA水平明显高于正常对照组织（P<0.001），CDCA8高表达患者的生存率明显低于低表达组（P<0.001）。随着肿瘤分期（P<0.001）、分级（P<0.001）和T分期（P<0.001）增加，肝细胞癌恶性程度增加，同时伴随CDCA8 mRNA水平增加。GSEA富集分析发现CDCA8高表达明显富集的通路包括细胞周期和有丝分裂。结论 CDCA8可作为肝细胞癌患者的预后分子标志物，深入研究后有望成为治疗的新靶点。

Abstract:

Objective Molecular markers related to the prognosis of hepatocellular carcinoma are essential for improving the quality of life of patients and improving the therapeutic efficacy. This study aims to investigate the effect of cell division cycle associated 8 （CDCA8） on the prognosis of hepatocellular carcinoma and its potential molecular mechanism.Methods The transcriptome data of 432 cases of hepatocellular carcinoma and the clinical information of the corresponding patients were downloaded from The Cancer Genome Atlas （TCGA） database. The differences of CDCA8 mRNA in tumor tissues and normal tissues were analyzed. The patients with hepatocellular carcinoma were divided into high expression group and low expression group according to the median CDCA8 mRNA，and the survival curve was drawn. Kruskal test was used to analyze the correlation between CDCA8 and tumor stage，grade and T stage. Univariate and multivariate Cox regression analysis were used to investigate whether CDCA8 could be used as an independent prognostic factor for patients with hepatocellular carcinoma. The potential molecular mechanism of CDCA8 in hepatocellular carcinoma was explored using gene set enrichment analysis （GSEA）.Results The mRNA level of CDCA8 in tumor tissues was significantly higher than that in control tissues （P<0.001），and the survival rate of patients with high CDCA8 expression was significantly lower than that of those with low expression （P<0.001）. As tumor stage （P<0.001），grade （P<0.001） and T stage （P<0.001） increase，the degree of malignancy of hepatocellular carcinoma increases，accompanied by an increase of the mRNA level of CDCA8. GSEA revealed significant pathways for CDCA8 overexpression including cell cycle and mitosis.Conclusion CDCA8 can be used as a prognostic molecular marker for patients with hepatocellular carcinoma，and it is expected to become a new target after in-depth study.