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中国癌症防治杂志

中国癌症防治杂志 ›› 2021, Vol. 13 ›› Issue (2): 183-189.doi: 10.3969/j.issn.1674-5671.2021.02.13

• 临床研究 • 上一篇    下一篇

BRCA1基因miRNA结合位点多态性与肝细胞癌术后总生存期的关联研究 

  

  1. 广西医科大学公共卫生学院；广西医科大学附属肿瘤医院；广西医科大学基础医学院
  • 出版日期:2021-04-25 发布日期:2021-04-30
  • 通讯作者: 余红平 E-mail：yuhongping@stu.gxmu.edu.cn

Association between polymorphisms in miRNA binding site of BRCA1 gene and overall survival of hepatocellular carcinoma after operation

  1.  
  • Online:2021-04-25 Published:2021-04-30
  • Supported by:
    国家自然科学基金项目（81460516）；广西重点研发计划项目（桂科AA18221001; 桂科AB18050020）;广西自然科学基金项目（2018GXNSFDA050012）；上海吴孟超医学科技基金项目（JJHXM-2019042）

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摘要： 目的 探讨BRCA1基因microRNA（miRNA）结合位点上的单核苷酸多态性对肝细胞癌（hepatocellular carcinoma，HCC）患者术后总生存期（overall survival，OS）的影响。方法 纳入2004年6月—2013年12月于广西医科大学附属肿瘤医院接受根治术切除的363例HCC患者为研究对象，采用Cox比例风险模型、Kaplan-Meier法分析BRCA1基因miRNA结合位点多态性与HCC患者术后OS的关系。结果 BRCA1 3'-UTR miRNA结合位点上的rs8176318（C>A）与HCC患者术后OS显著相关。在隐性模型下校正乙型肝炎病毒（hepatitis B virus，HBV）感染、BCLC分期、肿瘤直径、癌栓等因素后，Cox比例风险回归分析结果显示，与携带rs8176318 CC/CA基因型的HCC患者相比，携带AA基因型患者的死亡风险显著降低（HR=0.675，95%CI：0.494~0.922，P=0.014）。Kaplan-Meier分析结果显示，携带AA基因型的HCC患者比携带CC/CA基因型患者中位OS明显延长（46.1个月 vs 33.8个月，P=0.049）。利用GTEx数据库进行表达数量性状基因座分析，发现在肝脏组织中rs8176318 A等位基因与BRCA1 mRNA较低的表达水平相关（P<0.001）。结论 BRCA1 rs8176318可能影响HCC患者术后的生存结局，A等位基因与患者术后较低死亡风险有关，这一结果需要更大样本量的多中心研究验证。

关键词: 肝细胞癌, BRCA1, microRNA, 单核苷酸多态性, 总生存期

Abstract: Objective To investigate the effect of single nucleotide polymorphism (SNP) in microRNA (miRNA) binding site of BRCA1 gene on the overall survival (OS) of patients with hepatocellular carcinoma (HCC) after operation. Methods A total of 363 HCC patients with undergone radical surgery resection in the Guangxi Medical University Cancer Hospital from June 2004 to December 2013 were included. The Cox proportional hazard model and the Kaplan-Meier method were used to analysis the association between polymorphisms in miRNA binding site of BRCA1 gene and OS of patients with HCC after operation. Results The SNP rs8176318(C>A) in the miRNA binding site of BRCA1 gene was significantly associated with the OS of HCC patients after operation. In the recessive model, after adjusting for hepatitis B virus (HBV) infection, BCLC stage, tumor diameter, tumor thrombus and other factors, the Cox regression analysis showed that HCC patients carrying rs8176318 AA genotypes had a significantly decreased risk of death when compared with those carrying CC/CA genotype (HR=0.675, 95%CI = 0.494-0.922, P=0.014). The Kaplan-Meier curve showed that the median OS of HCC patients with AA genotype was significantly longer than that with CC/CA genotype (46.1 months vs 33.8 months, P=0.049). Using the GTEX database for quantitative trait locus analysis, the rs8176318 A allele was associated with lower BRCA1 mRNA expression levels in liver tissues (P<0.001). Conclusions BRCA1 rs8176318 polymorphism is associated with a lower survival outcomes in patients with HCC after operation, and the A allele is associated with a lower risk of death after operation, but the result needs to be verified by a multi-center study with a larger sample size.

Key words: Hepatocellular carcinoma, BRCA1, microRNA, Single nucleotide polymorphism, Overall survival

中图分类号: 

  • R735.7