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KRAS基因突变对经肝动脉化疗栓塞术治疗的中晚期原发性肝癌患者预后的预测价值

刘旭初 覃世运 陈丽君 陈娟 尤晓光

引用本文:
Citation:

KRAS基因突变对经肝动脉化疗栓塞术治疗的中晚期原发性肝癌患者预后的预测价值

DOI: 10.3969/j.issn.1001-5256.2022.11.015
基金项目: 

海南省重点研发科技发展项目 SQ2019KJHZ0073

伦理学声明:本研究方案于2017年1月8日经海南省第三人民医院伦理委员会审批,批号:伦(审)2017-09,所纳入患者均签署知情同意书。
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。
作者贡献声明:刘旭初、覃世运、陈丽君、陈娟、尤晓光负责课题设计,资料分析,撰写论文;刘旭初负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    刘旭初,273286268@qq.com

Prognostic value of KRAS mutations in patients with advanced primary liver cancer treated with transcatheter arterial chemoembolization

Research funding: 

Key R&D Technology Development Projects in Hainan Province SQ2019KJHZ0073

More Information
  • 摘要:   目的  探讨KRAS基因状态对经肝动脉化疗栓塞(TACE)治疗中晚期肝癌患者预后的预测价值。  方法  选择2017年4月—2020年5月在海南省第三人民医院接受TACE治疗的中晚期肝癌患者97例为研究对象。检测患者KRAS基因突变状态,并分析KRAS基因突变状态与患者TACE治疗预后的关系。计量资料两组间比较采用t检验,计数资料两组间比较采用χ2检验,生存分析绘制Kaplan-Meier生存曲线,生存曲线比较采用Log-rank检验,对可能影响患者预后的各因素进行Cox回归分析。  结果  97例患者中共检出KRAS基因突变患者34例(35.05%),其中检出12号密码子突变患者21例(61.76%),13号密码子突变患者13例(38.24%)。KRAS基因突变与患者肝硬化、肝内转移、肿瘤数目均显著相关(χ2值分别为0.035、3.965、6.593,P值均<0.05)。Kaplan-Meier生存分析结果显示,KRAS基因野生型患者无进展生存期及总体生存时间均显著优于KRAS突变型(χ2值分别为4.465、4.280,P值均<0.05)。Cox分析结果显示,KRAS基因状态、肝内转移、肿瘤数目、BCLC分期进入回归模型为影响患者总体生存预后的重要因素(P值均<0.05)。  结论  KRAS基因突变在肝癌患者中较为常见,KRAS基因突变与患者TACE术后不良预后密切相关,可成为患者临床预后监测的潜在指标。

     

  • 图  1  KRAS基因12、13密码子序列突变图谱

    注:a, KRAS基因12、13密码子野生型基因序列;b, KRAS基因12密码子GGT→GAT突变;c, KRAS基因12密码子GGT→GTT突变;d, KRAS基因13密码子GGC→GAC突变。

    Figure  1.  Mutation map of KRAS gene codons 12 and 13

    图  2  KRAS基因状态与患者PFS的关系

    Figure  2.  Relationship between KRAS gene status and progression-free survival analysis of patients

    图  3  KRAS基因状态与患者OS的关系

    Figure  3.  Relationship between KRAS gene status and overall survival analysis of patients

    表  1  KRAS基因突变状态与患者临床特征的关系

    Table  1.   The relationship between KRAS gene mutation status and clinical characteristics of patients

    临床资料 KRAS突变型
    (n=34)
    KRAS野生型
    (n=63)
    统计值 P
    性别(例) χ2=0.370 0.543
      男 20 41
      女 14 22
    年龄(岁) 55.12±14.21 56.93±10.04 t=0.730 0.468
    乙型肝炎病史(例) χ2=0.057 0.811
      阴性 30 56
      阳性 4 7
    ALT(U/L) 49.85±14.20 51.24±15.22 t=0.439 0.662
    凝血酶原时间(s) 12.83±1.84 13.02±2.10 t=0.443 0.659
    总胆红素(mmol/L) 17.94±3.73 18.05±3.16 t=0.153 0.878
    白蛋白(g/L) 40.27±6.49 40.53±5.98 t=0.198 0.843
    AFP(ng/L) 438.95±109.32 409.64±97.58 t=1.353 0.179
    肿瘤大小(cm) 7.39±2.30 7.02±2.15 t=0.789 0.432
    肝硬化(例) χ2=0.035 0.852
      有 27 49
      无 7 14
    肝内转移(例) χ2=3.965 0.047
      有 16 17
      无 18 46
    肿瘤数目(例) χ2=6.593 0.010
      单个 23 56
      多个 11 7
    腹水(例) χ2=0.057 0.811
      无 31 55
      有 3 8
    Child-Pugh分级(例) χ2=0.056 0.812
      A 24 43
      B 10 20
    BCLC分期(例) χ2=0.074 0.785
      B 22 39
      C 12 24
    下载: 导出CSV

    表  2  影响患者预后的Cox分析

    Table  2.   Cox analysis affecting patient outcomes

    自变量 RR 95%CI P
    性别(男性=0,女性=1) 2.734 0.983~7.935 0.283
    年龄(≥60岁=0,<60岁=1) 3.038 0.627~10.293 0.276
    KRAS基因状态(突变型=0,野生型=1) 18.273 5.584~98.305 0.001
    乙型肝炎病史(有=0,无=1) 5.484 0.719~9.380 0.193
    ALT(≥40 U/L=0,<40 U/L=1) 2.079 0.417~12.953 0.389
    凝血酶原时间(≥12 s=0,<12 s=1) 1.092 0.271~9.182 0.849
    总胆红素(≥18 nmol/L=0,<18
    nmol/L=1)
    1.684 0.495~7.293 0.711
    白蛋白(≥40 g/L=0,<40 g/L=1) 2.087 0.408~11.235 0.419
    AFP(≥400 ng/L=0,<400 ng/L=1) 2.193 0.602~11.293 0.619
    肿瘤大小(≥7 cm=0,<7 cm=1) 2.183 0.485~7.304 0.280
    肝硬化(有=0,无=1) 1.804 0.198~10.237 0.695
    肝内转移(有=0,无=1) 11.475 3.029~56.490 0.018
    肿瘤数目(单发=0,多发=1) 10.038 2.973~19.328 0.021
    腹水(有=0,无=1) 2.013 0.421~8.106 0.174
    Child-Pugh分级(A=0,B=1) 2.189 0.569~7.491 0.209
    BCLC分期(B=0,C=1) 12.384 2.385~29.305 0.011
    下载: 导出CSV
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