中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

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
  • [1] LI X, RAMADORI P, PFISTER D, et al. The immunological and metabolic landscape in primary and metastatic liver cancer[J]. Nat Rev Cancer, 2021, 21(9): 541-557. DOI: 10.1038/s41568-021-00383-9.
    [2] YU SX, ZHOU WP. Progress and hot spots of comprehensive treatment for primary liver cancer[J]. Chin J Dig Surg, 2021, 20(2): 163-170. DOI: 10.3760/cma.j.cn115610-20201211-00776.

    袁声贤, 周伟平. 原发性肝癌综合治疗的进展和热点[J]. 中华消化外科杂志, 2021, 20(2): 163-170. DOI: 10.3760/cma.j.cn115610-20201211-00776.
    [3] LIU CX, CHANG K, NA WL, et al. Role of differential expression and regulatory mechanism of miR-152-3 p target proteins in the recurrence of hepa-tocellular carcinoma[J]. J Clin Hepatol, 2021, 37(2): 364-369. DOI: 10.3969/j.issn.1001-5256.2021.02.023.

    刘晨霞, 常凯, 那琬琳, 等. miR-152-3p靶蛋白差异表达及调控机制在肝癌复发中的作用[J]. 临床肝胆病杂志, 2021, 37(2): 364-369. DOI: 10.3969/j.issn.1001-5256.2021.02.023.
    [4] BLACKBURN H, WEST S. Management of postembolization syndrome following hepatic transarterial chemoembolization for primary or metastatic liver cancer[J]. Cancer Nurs, 2016, 39(5): E1-E18. DOI: 10.1097/NCC.0000000000000302.
    [5] CHENG YR, YAN D, YANG JD, et al. Effect of hepatic artery chemoembolization combined with sorafenib in the treatment of primary liver cancer and its influence on patients' immune function[J]. Clin J Med Offic, 2021, 49(3): 290-291. DOI: 10.16680/j.1671-3826.2021.03.16.

    程瑜蓉, 严冬, 杨建东, 等. 肝动脉栓塞化疗联合索拉非尼在原发性肝癌治疗中应用效果及对患者免疫功能影响[J]. 临床军医杂志, 2021, 49(3): 290-291. DOI: 10.16680/j.1671-3826.2021.03.16.
    [6] RECK M, MOK T, NISHIO M, et al. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial[J]. Lancet Respir Med, 2019, 7(5): 387-401. DOI: 10.1016/S2213-2600(19)30084-0.
    [7] CUI FQ, LI T, WANG Z, et al. A pilot study on cetuximab and KRAS gene mutation in treatment of patients with primary liver can-cer[J]. J Prac Hepatol, 2019, 22(4): 565-568. DOI: 10.3969/j.issn.1672-5069.2019.04.029.

    崔发强, 李涛, 王铮, 等. 原发性肝癌患者外周血KRAS基因水平及其对西妥昔单克隆抗体治疗疗效的影响[J]. 实用肝脏病杂志, 2019, 22(4): 565-568. DOI: 10.3969/j.issn.1672-5069.2019.04.029.
    [8] PAN CF, ZHAO SK, LI Y, et al. Mutation study of related genes in non-small cell lung cancer drug targeting sites[J]. Hainan Med J, 2018, 29(19): 2696-2698. DOI: 10.3969/j.issn.1003-6350.2018.19.009.

    潘长芳, 赵胜科, 李洋, 等. 非小细胞肺癌药物靶向位点的相关基因突变研究[J]. 海南医学, 2018, 29(19): 2696-2698. DOI: 10.3969/j.issn.1003-6350.2018.19.009.
    [9] WU ST. Application of contrast-enhanced CT Scan in curative effect evaluation of primary hepatocellular carcinoma after TACE[J]. Chin J CT and MRI, 2022, 20(3): 91-93. DOI: 10.3969/j.issn.1672-5131.2022.03.030.

    吴水天. CT增强扫描在评估原发性肝细胞肝癌TACE术后疗效中的应用[J]. 中国CT和MRI杂志, 2022, 20(3): 91-93. DOI: 10.3969/j.issn.1672-5131.2022.03.030.
    [10] KIM D, LEE JH, MOON H, et al. Development and evaluation of an ultrasound-triggered microbubble combined transarterial chemoembolization (TACE) formulation on rabbit VX2 liver cancer model[J]. Theranostics, 2021, 11(1): 79-92. DOI: 10.7150/thno.45348.
    [11] CHEN XW, JIANG JW, LIN FH. Longdan xiegan decoction in the treatment of embolism syndrome after interventional therapy on primary hepatocellular carcinoma[J]. J Nangjing Univ Tradit Chin Med, 2016, 32(3): 224-228. DOI: 10.14148/j.issn.1672-0482.2016.0224.

    陈学武, 姜靖雯, 林福煌. 龙胆泻肝汤治疗原发性肝癌TACE术后栓塞综合征的疗效观察[J]. 南京中医药大学学报, 2016, 32(3): 224-228. DOI: 10.14148/j.issn.1672-0482.2016.0224.
    [12] YOU GM, JING BL, PAN Q, et al. Compression hemostasis with Shunlin arterial hemostatic dressing for patients with hepatocellular carcinoma after transcatheter arterial chemoembolization: its clinical application and efficacy[J]. J Intervent Radiol, 2021, 30(5): 519-522. DOI: 10.3969/j.issn.1008-794X.2021.05.021.

    尤国美, 经碧玲, 潘琴, 等. 瞬灵动脉止血敷料压迫止血在肝癌TACE患者的临床应用与效果研究[J]. 介入放射学杂志, 2021, 30(5): 519-522. DOI: 10.3969/j.issn.1008-794X.2021.05.021.
    [13] LUO Y, JIANG Y. Comparison of efficiency of TACE plus HIFU and TACE alone on patients with primary liver cancer[J]. J Coll Physicians Surg Pak, 2019, 29(5): 414-417. DOI: 10.29271/jcpsp.2019.05.414.
    [14] VOGL TJ, MARKO C, LANGENBACH MC, et al. Transarterial chemoembolization of colorectal cancer liver metastasis: improved tumor response by DSM-TACE versus conventional TACE, a prospective, randomized, single-center trial[J]. Eur Radiol, 2021, 31(4): 2242-2251. DOI: 10.1007/s00330-020-07253-2.
    [15] ZHANG X, ZHOU J, ZHU DD, et al. CalliSpheres® drug-eluting beads (DEB) transarterial chemoembolization (TACE) is equally efficient and safe in liver cancer patients with different times of previous conventional TACE treatments: a result from CTILC study[J]. Clin Transl Oncol, 2019, 21(2): 167-177. DOI: 10.1007/s12094-018-1902-8.
    [16] AARTS BM, MUÑOZ F, WILDIERS H, et al. Intra-arterial therapies for liver metastatic breast cancer: a systematic review and meta-analysis[J]. Cardiovasc Intervent Radiol, 2021, 44(12): 1868-1882. DOI: 10.1007/s00270-021-02906-1.
    [17] SUN ZQ, JIANG CY, LI BP, et al. Clinical efficacy and adverse reactions of TACE combined with different doses of apatinib in the treatment of advanced liver cancer[J]. Chin J Gerontol, 2022, 42(3): 557-560. DOI: 10.3969/j.issn.1005-9202.2022.03.014.

    孙志强, 姜成毅, 李佰萍, 等. TACE联合不同剂量阿帕替尼治疗中晚期肝癌的临床疗效及不良反应[J]. 中国老年学杂志, 2022, 42(3): 557-560. DOI: 10.3969/j.issn.1005-9202.2022.03.014.
    [18] HUANG CS, YU W, WANG Q, et al. Clinical efficacy of sorafenib and TACE for primary liver cancer and its effect on bFGF and VEGF level[J]. Pract J Cancer, 2017, 32(6): 943-945. DOI: 10.3969/j.issn.1001-5930.2017.06.021

    黄长山, 余伟, 王谦, 等. 索拉菲尼与TACE联合治疗原发性肝癌的临床效果及对bFGF、VEGF水平的影响[J]. 实用癌症杂志, 2017, 32(6): 943-945. DOI: 10.3969/j.issn.1001-5930.2017.06.021.
    [19] YE PL, JIA HY, PENG L. Mechanism of action of GP73 in the regulation of liver cancer: An analysis based on transcriptome sequencing[J]. J Clin Hepatol, 2021, 37(8): 1861-1866. DOI: 10.3969/j.issn.1001-5256.2021.08.022.

    叶佩灵, 嘉红云, 彭亮. 转录组测序分析高尔基体蛋白73参与调控肝癌的作用机制[J]. 临床肝胆病杂志, 2021, 37(8): 1861-1866. DOI: 10.3969/j.issn.1001-5256.2021.08.022.
    [20] QIN L, ZHAN Z, WEI C, et al. Hsa-circRNA-G004213 promotes cisplatin sensitivity by regulating miR-513b-5p/PRPF39 in liver cancer[J]. Mol Med Rep, 2021, 23(6): 421. DOI: 10.3892/mmr.2021.12060.
    [21] YIN XL, XU Q. The clinical significance of KRAS and BRAF oncogene mutations in hepatocellular carcinoma[J]. J Modern Oncology, 2016, 24(15): 2419-2422. DOI: 10.3969/j.issn.1672-4992.2016.15.022.

    尹小兰, 许青. 原发性肝癌中KRAS及BRAF基因突变及其临床意义[J]. 现代肿瘤医学, 2016, 24(15): 2419-2422. DOI: 10.3969/j.issn.1672-4992.2016.15.022.
  • 加载中
图(3) / 表(2)
计量
  • 文章访问数:  349
  • HTML全文浏览量:  83
  • PDF下载量:  37
  • 被引次数: 0
出版历程
  • 收稿日期:  2022-04-12
  • 录用日期:  2022-06-25
  • 出版日期:  2022-11-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回