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中国全科医学 ›› 2018, Vol. 21 ›› Issue (18): 2190-2195.DOI: 10.3969/j.issn.1007-9572.2018.00.223

• 专题研究 • 上一篇    下一篇

染色体8q拷贝数变异与肝细胞癌患者术后总生存期的相关性及其靶基因筛选

赵昆1，徐菊英2，许青1，3*，朱忠政3*   

  1. 1.200072上海市，安徽医科大学上海临床学院　2.315040浙江省宁波市，中国人民解放军第一一三医院医务处　3.200072上海市，上海市第十人民医院肿瘤科
    *通信作者：许青，教授，主任医师；xuqingmd@tongji.edu.cn　朱忠政，教授，主任医师；E-mail：zzzhu1170@yeah.net
  • 出版日期:2018-06-20 发布日期:2018-06-20
  • 基金资助:
    南京军区医学科技创新课题（14ZD07，08MA023）；宁波市自然科学基金资助项目（2009A610126）；宁波市C50-社会发展科技攻关项目（2014C50072）

Association of Chromosome 8q Copy Number Aberration with Postoperative Overall Survival of Patients with Hepatocellular Carcinoma and Screening of Potential Target Genes　

  1. 1.Shanghai Clinical College of Anhui Medical University，Shanghai 200072，China
    2.Department of Medical Affairs，No.113 Hospital of People's Liberation Army，Ningbo 315040，China
    3.Department of Oncology，Shanghai Tenth People's Hospital，Shanghai 200072，China
    *Corresponding author：XU Qing，Professor，Chief physician；E-mail：xuqingmd@tongji.edu.cn；ZHU Zhong-zheng，Professor，Chief physician；E-mail：zzzhu1170@yeah.net
  • Published:2018-06-20 Online:2018-06-20

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摘要： 目的　探讨染色体8q拷贝数变异（CNA）与肝细胞癌（HCC）患者术后总生存期（OS）的关系，并筛选生存相关CNA内的潜在靶基因。方法　收集2007—2008年于第二军医大学附属东方肝胆外科医院手术住院的HCC患者187例为研究对象。收集患者一般资料，检测其染色体8q CNA、染色体8q24.13-24.3片段内50个已知基因mRNA表达水平；术后对患者进行随访，最终共66例患者完成随访。一般资料、染色体8q内各高频CNA（增益发生率>20%）片段与OS的相关性分析采用Log-rank检验；采用Cox比例风险回归模型分析OS的影响因素；生存曲线比较采用Log-rank检验；染色体8q24.13-24.3增益HCC患者和8q24.13-24.3无增益HCC患者基因mRNA表达水平比较采用Mann-Whitney U检验。结果　HCC患者糖尿病史、有无完整肿瘤包膜、TNM分期与OS有相关性（P<0.05）。单因素Cox比例风险回归模型分析结果显示，染色体8q24.13-24.3增益与OS有相关性（P<0.05）；多因素Cox比例风险回归模型分析结果显示，染色体8q24.13-24.3增益、有无糖尿病史、有无完整肿瘤包膜、TNM分期是OS的影响因素（P<0.05）。生存分析结果显示，染色体8q24.13-24.3增益HCC患者生存率低于染色体8q24.13-24.3无增益HCC患者（P<0.05）。染色体8q24.13-24.3增益HCC患者C8orf76、ATAD2、WDYHV1、FBXO32、TMEM65、TATDN1、ZNF572、SQLE、KIAA0196、NSMCE2、PVT1、FAM49B、ASAP1、NDRG1、ZFAT、KHDRBS3、EIF2C2 mRNA表达水平高于染色体8q24.13-24.3无增益HCC患者（P<0.000 1）。结论　染色体8q24.13-24.3增益与HCC患者OS有关，可作为HCC的一个预后预测因子。ATAD2、PVT1、NDRG1拷贝数依赖性表达上调可能参与了HCC不良预后的演进过程。

关键词: 癌, 肝细胞, 预后, DNA拷贝数变异, 基因表达

Abstract: Objective　To investigate the association of chromosome arm 8q copy number aberration （CNA） with postoperative overall survival （OS） of patients with hepatocellular carcinoma （HCC），and to screen for potential target genes in the survival-related CNA（s）．Methods　A total of 187 HCC patients who received operation in Eastern Hepatobiliary Surgery Hospital，Second Military Medical University from 2007 to 2008 and postoperative follow-up（66 completed the follow-up） were enrolled in the study.We collected their clinicopathological data as well as follow-up data，including the mRNA expression levels of 50 known genes in chromosome 8q24.13-24.3 segment.The associations of the clinicopathological factors and high-frequency CNA（s） （>20%） in chromosome arm 8q with OS were analyzed using the Log-rank test.The confounding factors for OS were analyzed using the Cox proportional hazards model.The survival curves were analyzed using the Kaplan-Meier method.The expression levels between the HCC patients with 8q24.13-24.3 gain and those without were compared by the Mann-Whitney U test.Results　Diabetes history，absence of complete tumoral capsule and advanced TNM stage were associated with OS（P<0.05）.Univariate Cox analysis showed that chromosome 8q24.13-24.3 gain was associated with OS（P<0.05）.Multivariate Cox analysis showed that 8q24.13-24.3 gain，diabetes history，absence of complete tumoral capsule and advanced TNM stage were prognostic factors for OS（P<0.05）.Survival analysis showed that the survival rate of the patients with 8q24.13-24.3 gain was lower than that of those without （P<0.05）.The mRNA expression levels of 17 genes in 8q24.13-24.3 including C8orf76，ATAD2，WDYHV1，FBXO32，TMEM65，TATDN1，ZNF572，SQLE，KIAA0196，NSMCE2，PVT1，FAM49B，ASAP1，NDRG1，ZFAT，KHDRBS3 and EIF2C2 were significantly increased in patients with 8q24.13-24.3 gain compared to those without （P<0.000 1）.Conclusion　Copy number gain at 8q24.13-24.3 is a potential prognostic marker for reduced OS for HCC patients，and DNA copy-dependent upregulation of the genes ATAD2，PVT1 and NDRG1 may contribute to the 8q24.13-24.3 gain-related poor prognosis.

 

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