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结节性硬化基因1/2突变与肝细胞癌进展及预后的关系

张勇 毛正发

张勇, 毛正发. 结节性硬化基因1/2突变与肝细胞癌进展及预后的关系[J]. 临床肝胆病杂志, 2021, 37(1): 84-88. DOI: 10.3969/j.issn.1001-5256.2021.01.017
引用本文: 张勇, 毛正发. 结节性硬化基因1/2突变与肝细胞癌进展及预后的关系[J]. 临床肝胆病杂志, 2021, 37(1): 84-88. DOI: 10.3969/j.issn.1001-5256.2021.01.017
ZHANG Y, MAO ZF. Association of tuberous sclerosis gene 1/2 mutations with the progression of hepatocellular carcinoma and prognosis[J]. J Clin Hepatol, 2021, 37(1): 84-88. DOI: 10.3969/j.issn.1001-5256.2021.01.017
Citation: ZHANG Y, MAO ZF. Association of tuberous sclerosis gene 1/2 mutations with the progression of hepatocellular carcinoma and prognosis[J]. J Clin Hepatol, 2021, 37(1): 84-88. DOI: 10.3969/j.issn.1001-5256.2021.01.017

结节性硬化基因1/2突变与肝细胞癌进展及预后的关系

DOI: 10.3969/j.issn.1001-5256.2021.01.017
基金项目: 

国家自然科学基金 81502372

详细信息
    作者简介:

    张勇(1978—),男,副主任医师,主要从事肝胆病方面的研究

    通讯作者:

    毛正发,2630698662@qq.com

  • 利益冲突声明:本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突,特此声明。
  • 作者贡献声明:张勇负责课题设计,资料分析,撰写论文;毛正发负责收集数据,修改论文;张勇、毛正发负责拟定写作思路,指导撰写文章并最后定稿。
  • 中图分类号: R735.7

Association of tuberous sclerosis gene 1/2 mutations with the progression of hepatocellular carcinoma and prognosis

  • 摘要:   目的  探讨肝细胞癌(HCC)患者结节性硬化基因1/2(TSC1/2)突变与HCC严重程度及预后的关系,为HCC的诊断及治疗提供可行性依据。  方法  选取2012年1月—2020年1月江苏大学附属医院收治的HCC患者492例,其中59例患者出现TSC1/2基因突变(TSC1突变20例,TSC2突变41例,共同突变2例),分析TSC1/2突变组患者的临床特征,及TSC1/2突变与HCC临床分期相关性。对35例突变组和35例未突变组患者进行3年随访,观察TSC1/2突变对HCC预后的影响。计数资料两组间比较采用χ2检验;等级资料两组间比较采用Kruskal-Wallis H秩和检验;采用多元logistic回归分析相关性,随访资料采用Kaplan-Meier生存分析。  结果  492例HCC患者中,TSC1/2基因总体突变率为11.99%。TSC1、TSC2基因突变组患者性别、年龄、Child-Pugh评分及肿瘤大小与未突变组相较差异均无统计学意义(P值均>0.05),两组肿瘤个数、肝外转移情况及PS评分比较差异均有统计学意义(P值均<0.05)。logistic回归分析结果显示,TSC1/TSC2基因突变与HCC临床分期严重程度呈正相关(OR=1.706,P<0.05)。随访结果显示,TSC1/2突变组患者的生存率明显低于未突变组,前者3年病死率高达60.3%,与未突变组(38.6%)比较差异有统计学意义(χ2=3.923, P<0.05)。  结论  TSC1/2基因突变可能早期预测HCC的恶性进展,TSC1/2突变的患者预后更差,应用基因突变靶向药物治疗对于延缓HCC发展可能具有一定疗效。
  • 图  1  TSC1/2突变组与未突变组患者生存情况

    表  1  TSC1/2基因突变患者临床特征比较

    项目 TSC1 TSC2
    突变(n=20) 未突变(n=472) χ2 P 突变(n=41) 未突变(n=451) χ2 P
    性别[例(%)] 0.80 >0.05 1.08 >0.05
      男 14(70) 344(73) 27(66) 331(73)
      女 6(30) 128(27) 14(34) 120(27)
    年龄[例(%)] 0.01 >0.05 0.12 >0.05
      40~60岁 12(60) 284(61) 25(61) 271(60)
      60~75岁 8(40) 188(39) 16(39) 180(40)
    肿瘤大小[例(%)] 1.92 >0.05 0.25 >0.05
      ≥5个 13(65) 309(65) 26(63) 296(66)
      <5个 7(35) 163(35) 15(37) 155(34)
    肿瘤个数[例(%)] 29.90 <0.05 47.5 <0.05
      单个 1(05) 130(28) 5(12) 126(28)
      多个 19(95) 342(72) 36(88) 325(72)
    肝外转移[例(%)] 10.91 <0.05 7.56 <0.05
      否 7(35) 394(83) 17(41) 384(85)
      是 13(65) 78(17) 24(59) 67(15)
    PS评分[例(%)] 4.58 <0.05 4.19 <0.05
      0~2分 14(70) 410(87) 31(76) 393(87)
      3~4分 6(30) 62(13) 10(24) 58(13)
    Child-Pugh分级[例(%)] 4.39 >0.05 2.51 >0.05
      A级 1(5) 100(22) 8(10) 93(20)
      B级 14(70) 309(65) 24(68) 299(67)
      C级 5(25) 63(13) 9(22) 59(13)
    下载: 导出CSV

    表  2  随访的TSC1/2突变组与未突变组患者基本情况比较

    项目 TSC1/2未突变(n=35) TSC1/2突变(n=35) χ2 P
    性别[例(%)] 2.20 >0.05
      男 25(71) 19(54)
      女 10(29) 16(46)
    年龄[例(%)] 1.43 >0.05
      ≥40岁且<60岁 21(60) 16(46)
      ≥60岁且<75岁 14(40) 19(54)
    一级亲属[例(%)] 1.29 >0.05
      患肝癌 6(17) 10(29)
      无肝癌 29(83) 25(71)
    二级亲属[例(%)] 1.75 >0.05
      患肝癌 5(14) 2(6)
      无肝癌 30(86) 33(94)
    吸烟史[例(%)] 0.58 >0.05
      有 20(57) 19(54)
      无 15(43) 16(46)
    饮酒史[例(%)] 0.01 >0.05
      有 27(77) 23(66)
      无 8(23) 12(34)
    治疗方式[例(%)] 0.86 >0.05
      手术治疗 12(34) 15(43)
      介入治疗 18(51) 17(49)
      药物治疗 5(15) 3(8)
    肝病病程[例(%)] 2.69 >0.05
      ≤10年 6(17) 12(34)
      >10年 29(83) 23(66)
    下载: 导出CSV
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  • 收稿日期:  2020-07-02
  • 修回日期:  2020-08-03
  • 刊出日期:  2021-01-18
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