肝胆胰外科杂志 ›› 2019, Vol. 31 ›› Issue (10): 596-603.doi: 10.11952/j.issn.1007-1954.2019.10.006

• 论著 临床研究 • 上一篇    下一篇

CCNB1在原发性肝癌中的表达及临床意义

石小康,丁佑铭,汪斌,余斌,徐雨   

  1. (武汉大学人民医院   肝胆外科,湖北   武汉   430060)
  • 出版日期:2019-10-15 发布日期:2019-11-07
  • 通讯作者: 丁佑铭,主任医师,教授,E-mail:dingym@whu.edu.cn。
  • 作者简介:石小康(1994-),男,湖北孝感人,在读硕士

Expression and clinical significance of CCNB1 in primary hepatocellular carcinoma

SHI Xiaokang, DINGYou-ming, WANG Bin, YU Bin, XU Yu.   

  1. Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
  • Online:2019-10-15 Published:2019-11-07

摘要:

目的 探究细胞周期蛋白B1(CyclinB1,CCNB1)在原发性肝癌中的表达及临床意义。方法 从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载正常肝组织和肝癌组织中的CCNB1 mRNA二代测序数据及相应的临床病理资料,比较CCNB1 mRNA在肝癌及正常肝组织中的表达差异,同 时分析其表达水平与肝癌患者临床病理学特征及预后的关系,采用Cox回归法分析影响肝癌预后的危险 因素,利用生物信息学方法进行CCNB1共表达基因的GO和KECC富集分析。结果 CCNB1 mRNA在肝 癌组织中表达量明显高于正常肝组织(P<0.001);CCNB1 mRNA高表达与肝癌患者种族(P=0.005)、甲胎 蛋白(AFP)表达水平(P<0.0001)、病理分级(P<0.0001)、血管侵袭(P<0.0001)等显著相关,CCNB1 mRNA高表达组肝癌患者总生存期(overall survival,OS)(P=0.0015)和无病生存期(disease-free survival, DFS)(P=0.0004)短于 CCNB1 mRNA低表达组,差异有统计学意义。CCNB1 mRNA表达水平是影响肝癌 患者OS(HR 1.544,95%CI 1.052~2.266,P=0.027)和 DFS(HR 1.793,95%CI 1.277~2.517,P=0.001)的 独立危险因素。富集分析提示CCNB1共表达基因主要富集于细胞增殖、细胞周期、有丝分裂细胞周期的 G1/S转换、有丝分裂细胞周期的G2/M转换等功能及细胞周期调控、p53信号通路等通路。结论 CCNB1 在原发性肝癌组织中表达上调,其异常表达水平可能成为潜在的评估肝癌患者预后的生物标志物。

关键词: 原发性肝癌, 细胞周期蛋白B1, 癌症基因组图谱(TCGA)

Abstract:

objective  To investigate the expression of CyclinB1 (CCNB1) in primary hepatocellular carcinoma tissues and to evaluate its association with clinical pathological features. Methods  The mRNA expression data of CCNB1 and its clinical information were downloaded from The Cancer Genome Atlas (TCGA). Then the relationship between the mRNA expression of CCNB1 and its clinical pathological parameters was analyzed. Cox regression model was performed for the univariate and multivariate analysis of the factors affecting the prognosis of primary hepatocellular carcinoma. GO and KEGG pathway analysis of CCNB1 co-expressed genes were performed. Results  The mRNA expression level of CCNB1 in primary hepatocellular carcinoma was significantly higher than that in normal liver tissue (P<0.001). Moreover, its expression level was significantly correlated with race (P=0.005), AFP (P<0.0001), histological grade (P<0.0001), vascular invasion (P<0.0001) of patients. Kaplan-Meier survival analysis showed that the overall survival (P=0.0015) rate and disease-free survival rate (P=0.0004) in patients with CCNB1 high-expression was significantly lower than that in patients with CCNB1 low-expression. Univariate and multivariate analysis revealed that CCNB1 expression was independent prognostic indicator for poor OS (HR 1.544, 95%CI 1.052~2.266, P=0.027) and DFS (HR 1.793, 95%CI 1.277~2.517, P=0.001). GO and KEGG pathway analysis showed that CCNB1 co-expressed genes were associated with cell proliferation, cell cycle, G1/S transition of mitotic cell cycle, G2/M transition of mitotic cell cycle, p53 signaling pathway. Conclusion  CCNB1 is aberrantly expressed in primary hepatocellular carcinoma and its expression may be a diagnostic biomarker.

Key words: primary hepatocellular carcinoma, CyclinB1(CCNB1), The Cancer Genome Atlas (TCGA)

中图分类号: 

  • R735.7
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