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白蛋白-胆红素评分联合肝功能指标及CEA对结直肠癌肝转移的预测价值

樊万里 何栋 张树泽 陈刚 赵斌 程志斌

樊万里, 何栋, 张树泽, 陈刚, 赵斌, 程志斌. 白蛋白-胆红素评分联合肝功能指标及CEA对结直肠癌肝转移的预测价值[J]. 协和医学杂志, 2024, 15(1): 99-108. doi: 10.12290/xhyxzz.2023-0261
引用本文: 樊万里, 何栋, 张树泽, 陈刚, 赵斌, 程志斌. 白蛋白-胆红素评分联合肝功能指标及CEA对结直肠癌肝转移的预测价值[J]. 协和医学杂志, 2024, 15(1): 99-108. doi: 10.12290/xhyxzz.2023-0261
FAN Wanli, HE Dong, ZHANG Shuze, CHEN Gang, ZHAO Bin, CHENG Zhibin. Predictive Value of Albumin-Bilirubin Score Combined with Liver Function Index and CEA for Liver Metastasis of Colorectal Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2024, 15(1): 99-108. doi: 10.12290/xhyxzz.2023-0261
Citation: FAN Wanli, HE Dong, ZHANG Shuze, CHEN Gang, ZHAO Bin, CHENG Zhibin. Predictive Value of Albumin-Bilirubin Score Combined with Liver Function Index and CEA for Liver Metastasis of Colorectal Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2024, 15(1): 99-108. doi: 10.12290/xhyxzz.2023-0261

白蛋白-胆红素评分联合肝功能指标及CEA对结直肠癌肝转移的预测价值

doi: 10.12290/xhyxzz.2023-0261
基金项目: 

国家自然科学基金 82060508

甘肃省卫生行业计划 GSWSKY-2019-66

甘肃省卫生行业科研计划 GSWSKY2022-12

兰州大学第二医院“萃英科技创新”计划 2020QN-21

详细信息
    通讯作者:

    程志斌, E-mail: zhibin_cheng@hotmail.com

  • 中图分类号: R735.34;R446

Predictive Value of Albumin-Bilirubin Score Combined with Liver Function Index and CEA for Liver Metastasis of Colorectal Cancer

Funds: 

National Natural Science Foundation 82060508

Gansu Province Health Industry Plan GSWSKY-2019-66

Gansu Province Health Industry Research Project GSWSKY2022-12

"Cuiying Science and Technology Innovation" Project of the Second Hospital & Clinical Medical School, Lanzhou University 2020QN-21

More Information
  • 摘要:   目的  探讨白蛋白-胆红素(albumin-bilirubin, ALBI)评分联合肝功能指标及癌胚抗原(carcinoembryonic antigen, CEA)对结直肠癌肝转移的预测价值。  方法  回顾性分析2016年1月至2021年7月于兰州大学第二医院接受手术治疗且随访满24个月的结直肠癌患者临床资料, 依据随访结果将入组患者分为肝转移组和非肝转移组, 并按2∶1比例随机分为建模组与验证组。分析结直肠癌患者发生肝转移的风险因素, 采用Lasso-Logistic回归构建预测模型, 采用Bootstrap法进行内部验证, 应用受试者工作特征曲线、校准曲线和临床决策曲线评价预测模型的可靠性, 最后绘制列线图展示预测结果。  结果  共入选符合纳入和排除标准的结直肠癌患者195例, 其中建模组130例, 验证组65例; Lasso回归变量筛选及Logistic回归分析结果显示, ALBI评分(OR=8.062, 95% CI: 2.545~25.540)、丙氨酸氨基转移酶(alanine transaminase, ALT)(OR=1.037, 95% CI: 1.004~1.071)与CEA(OR=1.025, 95% CI: 1.008~1.043)是结直肠癌发生肝转移的独立预测因素; 建模组三者联合预测结直肠癌发生肝转移的曲线下面积(area under the curve, AUC)为0.921, 灵敏度为78.0%, 特异度为95.0%, C-index为0.921, H-L拟合度曲线χ2=0.851, P=0.654, 校准曲线斜率接近1, 提示该模型准确度较高, 临床决策曲线显示该模型具有良好的临床应用价值。对建模组数据采用Bootstrap法进行1000次重抽样的内部验证, 准确度为0.869, Kappa一致性为0.709, AUC为0.913;应用ALBI评分、ALT与CEA单独诊断结直肠癌肝转移时, CEA的AUC最大(0.897), 三者联合诊断结直肠癌肝转移的效能最高。验证组三者联合预测结直肠癌发生肝转移的AUC为0.918, 灵敏度为85.0%, 特异度为95.6%, C-index为0.918, H-L拟合度曲线χ2=0.586, P=0.746。  结论  ALBI评分、ALT与CEA对结直肠癌肝转移具有一定预测价值, 三者联合预测结直肠癌肝转移的效能较高, 通过其构建的风险预测模型具有良好的临床应用前景。
    作者贡献:樊万里负责资料收集和论文撰写;何栋、张树泽、陈刚、赵斌提供论文撰写意见;程志斌负责论文设计及审校。
    利益冲突:所有作者均声明不存在利益冲突
  • 图  1  研究对象入组流程图

    Figure  1.  Flowchart for enrollment of subjects

    图  2  基于Lasso回归的特征变量筛选

    A.十倍交叉验证图; B.收缩系数图

    Figure  2.  Feature variable selection based on Lasso regression

    A.Ten fold cross validation chart; B.Shrinkage coefficient chart

    图  3  模型预测结直肠癌肝转移的受试者工作特征曲线

    A.建模组;B.验证组

    Figure  3.  Receiver operating characteristic curve of the model predicting liver metastasis of colorectal cancer

    A.Modeling group; B.Verification group
    ALT、CEA、ALBI: 同表 1

    图  4  Lasso-Logistic回归模型校准曲线

    A.建模组;B.验证组

    Figure  4.  Calibration curves of the Lasso-Logistic regression model

    A.Modeling group; B.Verification group

    图  5  Lasso-Logistic回归模型临床决策曲线

    A.建模组;B.验证组

    Figure  5.  Decision curve analysis of the Lasso-Logistic regression model

    B.Modeling group; B.Verification group

    图  6  结直肠癌肝转移的列线图预测模型

    ALT、CEA、ALBI: 同表 1

    Figure  6.  Nomogram prediction model for liver metastasis of colorectal cancer

    表  1  肝转移组与非肝转移组的基线资料比较(n=195)

    Table  1.   Baseline data between liver metastasis group and non-liver metastasis group(n=195)

    指标 肝转移组(n=70) 非肝转移组(n=125) P
    年龄(x±s,岁) 58.3±12.5 61.7±12.0 0.067
    性别[n(%)] 0.865
      男 40(57.1) 73(58.4)
      女 30(42.9) 52(41.6)
    原发肿瘤位置[n(%)] 0.042
      结肠 38(54.3) 49(39.2)
      直肠 32(45.7) 76(60.8)
    BMI[M(P25, P75), kg/m2] 22.5(21.4, 24.7) 22.1(20.2, 25.0) 0.280
    TBIL[M(P25, P75), μmol/L] 14.9(11.6, 24.7) 12.8(9.4, 16.9) 0.001
    DBIL[M(P25, P75), μmol/L] 7.2(4.3, 10.6) 3.3(2.3, 5.4) <0.001
    IBIL[M(P25, P75), μmol/L] 9.3(5.2, 14.3) 8.8(6.0, 12.1) 0.642
    ALT[M(P25, P75), U/L] 31.5(16.0, 54.8) 17.0(10.0, 25.0) <0.001
    AST[M(P25, P75), U/L] 40.0(27.8, 87.3) 20.0(16.0, 25.5) <0.001
    AST/ALT[M(P25, P75)] 1.6(1.1, 2.2) 1.4(0.9, 1.7) 0.005
    TP[M(P25, P75), g/L] 65.1(58.9, 70.6) 69.4(64.3, 73.4) 0.001
    ALB[M(P25, P75), g/L] 36.3(29.5, 40.2) 41.4(38.3, 44.1) <0.001
    GLO[M(P25, P75), g/L] 29.3(24.7, 33.5) 28.3(24.0, 31.0) 0.124
    A/G(x±s) 1.2±0.4 1.5±0.3 <0.001
    GGT[M(P25, P75), U/L] 59.0(25.8, 148.0) 18.0(13.0, 25.5) <0.001
    ALP[M(P25, P75), U/L] 122.5(77.5, 211.0) 76.0(63.0, 90.5) <0.001
    AFP[M(P25, P75), μg/L] 2.6(1.6, 3.4) 2.5(1.8, 3.2) 0.845
    CEA[M(P25, P75), μg/L] 79.5(12.5, 476.0) 2.9(1.8, 5.9) <0.001
    CA125[M(P25, P75), U/mL] 21.3(11.0, 54.7) 11.1(7.9, 16.7) <0.001
    CA19-9[M(P25, P75), U/mL] 85.5(17.3, 801.7) 10.9(7.5, 17.0) <0.001
    ALBI评分[M(P25, P75), 分] -2.3(-2.7, -1.6) -2.8(-3.0, -2.6) <0.001
    BMI(body mass index):体质量指数;TBIL(total bilirubin):总胆红素;DBIL(direct bilirubin):直接胆红素;IBIL(indirect bilirubin):间接胆红素;ALT(alanine transaminase):丙氨酸氨基转移酶;AST(aspartate transaminase):天冬氨酸氨基转移酶;TP(total protein):总蛋白;ALB(albumin):白蛋白;GLO(globulin): 球蛋白;A/G(albumin/globulin):白球比;GGT(γ-glutamyle transpeptidase):γ-谷氨酰转移酶;ALP(alkaline phosphatase):碱性磷酸酶;AFP(alpha fetoprotein):甲胎蛋白;CEA(carcinoembryonic antigen):癌胚抗原;CA125(carbohydrate antigen 125):糖类抗原125;CA19-9(carbohydrate antigen19-9):糖类抗原19-9;ALBI(albumin-bilirubin):白蛋白-胆红素
    下载: 导出CSV

    表  2  建模组与验证组的基线资料比较(n=195)

    Table  2.   Baseline data between modeling group and validation group(n=195)

    指标 建模组(n=130) 验证组(n=65) P
    年龄(x±s,岁) 60.3±11.8 60.8±13.2 0.770
    性别[n(%)] 0.473
      男 73(56.2) 40(61.5)
      女 57(43.8) 25(38.5)
    原发肿瘤位置[n(%)] 0.222
      结肠 62(47.7) 25(38.5)
      直肠 68(52.3) 40(61.5)
    BMI[M(P25, P75), kg/m2] 22.3(20.3, 24.9) 22.0(20.6, 25.0) 0.992
    TBIL[M(P25, P75), μmol/L] 13.3(10.2, 18.0) 14.0(9.6, 18.7) 0.825
    DBIL[M(P25, P75), μmol/L] 4.7(2.8, 7.3) 3.9(2.7, 7.1) 0.462
    IBIL[M(P25, P75), μmol/L] 8.7(5.5, 11.9) 9.6(5.6, 13.0) 0.412
    ALT[M(P25, P75), U/L] 17.5(11.0, 31.0) 20.0(11.0, 33.0) 0.518
    AST[M(P25, P75), U/L] 24.5(17.0, 36.0) 24.0(17.5, 38.0) 0.846
    AST/ALT[M(P25, P75)] 1.4(0.9, 1.8) 1.4(0.9, 1.9) 0.715
    TP[M(P25, P75), g/L] 68.3(63.8, 72.9) 67.1(61.8, 73.0) 0.348
    ALB[M(P25, P75), g/L] 40.1(35.8, 43.5) 39.1(36.8, 42.7) 0.666
    GLO[M(P25, P75), g/L] 28.7(24.4, 32.4) 28.4(24.0, 31.4) 0.556
    A/G(x±s) 1.4±0.4 1.4±0.3 0.990
    GGT[M(P25, P75), U/L] 22.5(14.0, 51.3) 22.0(14.5, 40.5) 0.828
    ALP[M(P25, P75), U/L] 80.0(63.8, 111.0) 86.0(67.0, 110.0) 0.606
    AFP[M(P25, P75), μg/L] 2.5(1.7, 3.3) 2.7(1.6, 3.2) 0.607
    CEA[M(P25, P75), μg/L] 4.7(2.0, 33.3) 5.3(2.5, 35.3) 0.514
    CA125[M(P25, P75), U/mL] 12.6(8.6, 23.2) 13.2(9.1, 22.7) 0.790
    CA19-9[M(P25, P75), U/mL] 13.9(8.1, 52.6) 15.2(8.2, 52.4) 0.697
    ALBI评分[M(P25, P75), 分] -2.7(-2.9, -2.3) -2.7(-2.9, -2.4) 0.522
    BMI、TBIL、DBIL、IBIL、ALT、AST、TP、ALB、GLO、A/G、GGT、ALP、AFP、CEA、CA125、CA19-9、ALBI:同表 1
    下载: 导出CSV

    表  3  结直肠癌肝转移影响因素的多因素Logistic回归分析结果

    Table  3.   Multivariate Logistic regression analysis results of factors influencing liver metastasis of colorectal cancer

    变量 β 标准误差 Wald 自由度 P OR 95% CI
    下限 上限
    ALT(U/L) 0.036 0.017 4.734 1 0.030 1.037 1.004 1.071
    CEA(μg/L) 0.025 0.009 8.017 1 0.005 1.025 1.008 1.043
    ALBI评分(分) 2.087 0.588 12.588 1 0.000 8.062 2.545 25.540
    常数项 3.047 1.555 3.839 1 0.050 21.058 -
    ALT、CEA、ALBI:同表 1
    下载: 导出CSV

    表  4  建模组患者ALT、CEA和ALBI评分单独检测与联合检测的诊断效能比较

    Table  4.   Diagnostic efficacy between individual and combined detection of ALT, CEA, and ALBI score in modeling group

    检测指标 AUC 灵敏度(%) 特异度(%) P
    ALT 0.704 58.0 85.0 <0.001
    CEA 0.897 84.0 87.5 <0.001
    ALBI评分 0.825 84.0 72.5 <0.001
    ALT联合CEA 0.896 80.0 91.2 <0.001
    ALT联合ALBI评分 0.858 80.0 78.7 <0.001
    CEA联合ALBI评分 0.911 82.0 86.3 <0.001
    三者联合 0.921 78.0 95.0 <0.001
    ALT、CEA、ALBI:同表 1;AUC(area under the curve):曲线下面积
    下载: 导出CSV

    表  5  验证组患者ALT、CEA和ALBI评分单独检测与联合检测的诊断效能比较

    Table  5.   Diagnostic efficacy between individual and combined detection of ALT, CEA, and ALBI score in verification group

    检测指标 AUC 灵敏度(%) 特异度(%) P
    ALT 0.774 75.0 73.3 <0.001
    CEA 0.864 75.0 88.9 <0.001
    ALBI评分 0.659 45.0 97.8 0.042
    ALT联合CEA 0.916 85.0 95.6 <0.001
    ALT联合ALBI评分 0.784 60.0 91.1 <0.001
    CEA联合ALBI评分 0.834 70.0 100.0 <0.001
    三者联合 0.918 85.0 95.6 <0.001
    ALT、CEA、ALBI:同表 1;AUC:同表 4
    下载: 导出CSV
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出版历程
  • 收稿日期:  2023-05-31
  • 录用日期:  2023-08-01
  • 网络出版日期:  2023-08-15
  • 刊出日期:  2024-01-30

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