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炎症标志物对早期小肝癌行射频消融术预后的预测价值

楚伟可 吴雪 张鹏 冯婧 牛斌 周辉 宓余强 李萍

引用本文:
Citation:

炎症标志物对早期小肝癌行射频消融术预后的预测价值

DOI: 10.3969/j.issn.1001-5256.2022.04.020
基金项目: 

中国肝炎防治基金会王宝恩肝纤维化研究基金 (2021038)

伦理学声明:本研究于2019年12月25日通过天津市第二人民医院伦理委员会批准,批号:[2019]58。
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:楚伟可负责课题设计,数据收集分析,撰写论文;吴雪、张鹏、冯婧、牛斌、周辉参与收集数据,修改论文;宓余强负责指导写作思路;李萍负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    李萍, tjlplxg@163.com

Value of inflammatory biomarkers in predicting the prognosis of early small hepatocellular carcinoma after radiofrequency ablation

Research funding: 

Chinese Foundation for Hepatitis Prevention and Control (2021038)

More Information
    Corresponding author: LI Ping, tjlplxg@163.com (ORCID: 0000-0001-9930-6429)
  • 摘要:   目的  探讨中性粒细胞/淋巴细胞比值(NLR)、红细胞分布宽度/淋巴细胞比值(RLR)及淋巴细胞/单核细胞比值(LMR)在早期小肝癌射频消融术后的预后价值。  方法  选取2011年9月-2020年12月在天津市第二人民医院行射频消融术的132例初诊早期肝细胞癌(HCC)患者。收集患者术前资料并随访观察复发和生存情况。运用X-tile工具以5年生存率及无复发生存率确定NLR、RLR和LMR的最佳截断值并组合成为N-R-L评分, 并据此分为N-R-L 0分组(n=92)、N-R-L 1分组(n=29)和N-R-L 2分组(n=11)。计数资料3组间比较采用χ2检验。采用Kaplan-Meier方法绘制生存曲线, 并用log-rank检验对无复发生存率及总体生存率进行组间比较。单因素分析采用log-rank检验, 并将log-rank检验分析中具有统计学意义的因素纳入多因素Cox回归分析以确定无复发生存率与总生存率的危险因素。  结果  N-R-L 0分、N-R-L 1分和N-R-L 2分组的组间Child-Pugh分级、Alb比较差异均有统计学意义(χ2值分别为10.992、5.699, P值均 < 0.05)。3组的1、3和5年总体生存率分别为100%、96.3%、90.7%, 96.6%、60.4%、41.3%和81.8%、46.8%、15.6%(χ2=38.460, P < 0.000 1);3组的1、3和5年无复发生存率分别为76.9%、52.5%、33.3%, 42.9%、13.1%、0和11.1%、0、0(χ2=35.345, P < 0.000 1)。多因素Cox回归分析显示, 肿瘤直径≥ 2 cm(HR=2.10, 95%CI: 1.28~3.43, P=0.003; HR=3.67, 95%CI: 1.58~8.52, P=0.002)、N-R-L评分1分(HR=3.14, 95%CI: 1.81~5.46, P < 0.000 1; HR=8.27, 95%CI: 3.15~21.71, P < 0.000 1)以及N-R-L评分2分(HR=2.61, 95%CI: 1.06~6.42, P=0.037; HR=14.59, 95%CI: 3.96~53.78, P < 0.000 1)是无复发生存与总生存的独立预测因素。  结论  由NLR、RLR和LMR组合而成的全身炎症反应标志物N-R-L评分是早期小肝癌射频消融术后复发和生存的独立危险因素, 可作为有用的无创生物标志物, 与肿瘤特征联合用来预测早期HCC射频消融术后的复发和生存。

     

  • 图  1  对患者5年OS和RFS进行X-tile分析以确定NLR的最佳截断值

    注:a,OS面板图;b,OS人数分布直方图;c,NLR组OS比较;d,RFS面板图;e,RFS人数分布直方图;f,NLR组RFS比较。

    Figure  1.  X-tile analysis of 5-year OS and RFS was performed to determine the best cutoff value of NLR

    图  2  对患者5年OS和RFS进行X-tile分析以确定RLR的最佳截断值

    注:a,OS面板图;b,OS人数分布直方图;c,RLR组OS比较;d,RFS面板图;e,RFS人数分布直方图;f,RLR组RFS比较。

    Figure  2.  X-tile analysis of 5-year OS and RFS was performed to determine the best cutoff value of RLR

    图  3  对患者5年OS和RFS进行X-tile分析以确定LMR的最佳截断值

    注:a,OS面板图;b,OS人数分布直方图;c,LMR组OS比较;d,RFS面板图;e,RFS人数分布直方图;f,LMR组RFS比较。

    Figure  3.  X-tile analysis of 5-year OS and RFS was performed to determine the best cutoff value of LMR

    图  4  RFA术后N-R-L分组的RFS率和OS率比较

    Figure  4.  Comparison of RFS and OS in N-R-L group after RFA

    表  1  N-R-L评分的计分及分组方式

    Table  1.   Scoring and grouping of N-R-L score

    变量 得分
    NLR
      <4.1 0
      ≥4.1 1
    RLR
      <18.3 0
      ≥18.3 1
    LMR
      <6 0
      ≥6 1
    N-R-L
      NLR+RLR+LMR=0 0
      NLR+RLR+LMR=1 1
      NLR+RLR+LMR=2 2
    注:N-R-L,NLR、RLR和LMR三项评分之和。
    下载: 导出CSV

    表  2  术前N-R-L分组患者的临床特征

    Table  2.   Clinical characteristics of patients in preoperative N-R-L group

    临床特征 N-R-L 0分组(n=92) N-R-L 1分组(n=29) N-R-L 2分组(n=11) χ2 P
    性别[例(%)] 0.545 0.762
      男 66(71.7) 21(72.4) 9(81.8)
      女 26(28.3) 8(27.6) 2(18.2)
    年龄[例(%)] 0.371 0.831
      <60岁 48(52.2) 17(58.6) 6(54.5)
      ≥ 60岁 44(47.8) 12(41.4) 5(45.5)
    BMI[例(%)] 2.024 0.363
      <24 kg/m2 42(45.7) 9(31.0) 5(45.5)
      ≥24 kg/m2 50(54.3) 20(69.0) 6(54.5)
    Child-Pugh分级[例(%)] 10.992 0.001
      A级 81(88.0) 26(89.7) 4(36.4)
      B级 11(12.0) 3(10.3) 7(63.6)
    BCLC分期[例(%)] 3.640 0.056
      0期 18(19.6) 3(10.3) 0
      A期 74(80.4) 26(89.7) 11(100)
    肿瘤直径[例(%)] 3.876 0.144
      <2 cm 53(57.6) 17(58.6) 3(27.3)
      ≥2 cm 39(42.4) 12(41.4) 8(72.7)
    HBV感染[例(%)] 1.601 0.449
      否 22(23.9) 5(17.2) 4(36.4)
      是 70(76.1) 24(82.8) 7(63.6)
    HCV感染[例(%)] 1.029 0.598
      否 76(82.6) 22(75.9) 8(71.7)
      是 16(17.4) 7(24.1) 3(27.3)
    MAFLD[例(%)] 0.367 0.832
      否 56(60.9) 16(55.2) 7(63.6)
      是 36(39.1) 13(44.8) 4(36.4)
    AFP[例(%)] 1.266 0.531
      <15 ng/mL 59(64.1) 21(72.4) 6(54.5)
      ≥15 ng/mL 33(35.9) 8(27.6) 5(45.5)
    ALBI分级[例(%)] 2.845 0.092
      1级 54(58.7) 16(55.2) 5(45.4)
      2级 36(39.1) 13(44.8) 3(27.3)
      3级 2(2.2) 0 3(27.3)
    TBil[例(%)] 0.904 0.636
      ≤20 μmol/L 55(59.8) 16(55.2) 5(45.5)
      >20 μmol/L 37(40.2) 13(44.8) 6(54.5)
    Alb[例(%)] 5.699 0.017
      ≥35 g/L 82(89.1) 23(79.3) 7(63.6)
      <35 g/L 10(10.9) 6(20.7) 4(36.4)
    ALT[例(%)] 0.109 0.741
      ≤50 U/L 76(82.6) 28(96.6) 7(63.6)
      >50 U/L 16(17.4) 1(3.4) 4(36.4)
    AST[例(%)] 1.572 0.456
      ≤40 U/L 71(77.2) 24(82.8) 7(63.6)
      >40 U/L 21(22.8) 5(17.2) 4(36.4)
    MELD评分[例(%)] 3.022 0.221
      <9分 65(70.7) 18(62.1) 5(45.5)
      ≥9分 27(29.3) 11(37.9) 6(54.5)
    注:ALBI分级,白蛋白-胆红素分级。
    下载: 导出CSV

    表  3  Cox回归分析RFS率的影响因素

    Table  3.   Results of RFS by Cox regression analysis

    变量 单因素分析 多因素分析
    HR(95%CI) P HR(95%CI) P
    性别(男/女) 1.97(1.14~3.40) 0.015 1.55(0.87~2.76) 0.136
    BMI(≥24 kg/m2/<24 kg/m2) 1.22(0.77~1.92) 0.402
    MAFLD(是/否) 1.03(0.65~1.61) 0.916
    Child-Pugh分级(B级/A级) 2.58(1.50~4.45) 0.001 1.28(0.56~2.91) 0.564
    肿瘤直径(≥2 cm/<2 cm) 2.28(1.43~3.62) 0.001 2.10(1.28~3.43) 0.003
    BCLC分期(A期/0期) 2.06(0.89~4.75) 0.090
    ALT(>50 U/L/≤50 U/L) 1.41(0.78~2.57) 0.260
    AST(>40 U/L/≤40 U/L) 1.63(0.98~2.70) 0.058
    TBil(≤20 μmol/L/>20 μmol/L) 1.69(1.07~2.65) 0.024 1.60(0.96~2.67) 0.074
    Alb(<35 g/L/≥35 g/L) 2.45(1.45~4.12) 0.001 1.01(0.44~2.32) 0.974
    AFP(>400 ng/mL/≤400 ng/mL) 0.81(0.33~2.01) 0.650
    ALBI分级(ref: 1级)
      2级 1.25(0.79~2.00) 0.341 0.92(0.49~1.70) 0.781
      3级 4.15(1.61~10.70) 0.003 1.91(0.48~7.59) 0.356
    MELD评分(>9分/≤9分) 1.44(0.91~2.28) 0.124
    N-R-L得分(ref: 0分)
      1分 3.13(1.89~5.20) <0.000 1 3.14(1.81~5.46) <0.000 1
      2分 4.99(2.40~10.37) <0.000 1 2.61(1.06~6.42) 0.037
    下载: 导出CSV

    表  4  Cox回归分析OS率的影响因素

    Table  4.   Results of OS by Cox regression analysis

    变量 单因素分析 多因素分析
    HR(95%CI) P HR(95%CI) P
    性别(男/女) 2.17(0.88~5.33) 0.093
    BMI(≥24 kg/m2/<24 kg/m2) 1.64(0.78~3.44) 0.191
    MAFLD(是/否) 1.20(0.58~2.51) 0.620
    Child-Pugh分级(B级/A级) 3.54(1.52~8.25) 0.003 0.99(0.28~3.52) 0.987
    肿瘤直径(≥2 cm/<2 cm) 2.89(1.36~6.14) 0.006 3.67(1.58~8.52) 0.002
    BCLC分期(A期/0期) 1.10(0.33~3.63) 0.880
    ALT(>50 U/L/≤50 U/L) 1.21(0.46~3.17) 0.705
    AST(>40 U/L/≤40 U/L) 1.30(0.58~2.94) 0.530
    TBil(≤20 μmol/L/>20 μmol/L) 2.27(1.08~4.76) 0.030 1.97(0.82~4.77) 0.132
    Alb(<35 g/L/≥35 g/L) 3.49(1.58~7.74) 0.002 1.36(0.36~5.09) 0.649
    AFP(>400 ng/mL/≤400 ng/mL) 1.35(0.41~4.50) 0.621
    ALBI分级(ref: 1级)
      2级 1.67(0.78~3.56) 0.184 0.97(0.35~2.65) 0.950
      3级 12.94(2.55~65.68) 0.002 2.11(0.25~17.94) 0.495
    MELD评分(>9分/≤9分) 1.59(0.75~3.33) 0.224
    N-R-L得分(ref: 0分)
      1分 6.92(2.82~17.00) <0.000 1 8.27(3.15~21.71) <0.000 1
      2分 13.50(4.68~38.91) <0.000 1 14.59(3.96~53.78) <0.000 1
    下载: 导出CSV
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