Research ArticleOriginal Article

Diagnostic value of 5 serum biomarkers for hepatocellular carcinoma with different epidemiological backgrounds: A large-scale, retrospective study

Dongming Liu, Yi Luo, Lu Chen, Liwei Chen, Duo Zuo, Yueguo Li, Xiaofang Zhang, Jing Wu, Qing Xi, Guangtao Li, Lisha Qi, Xiaofen Yue, Xiehua Zhang, Zhuoyu Sun, Ning Zhang, Tianqiang Song, Wei Lu and Hua Guo
Cancer Biology & Medicine February 2021, 18 (1) 256-270; DOI: https://doi.org/10.20892/j.issn.2095-3941.2020.0207

Article Figures & Data

Figures

  • Figure 1
    Figure 1

    The median plasma levels of AFP (A), AFU (B), GPC3 (C), GGT-II (D), and HGF (E) in the test cohort and AFP (F) and AFU (G) in the validation cohort. HC, healthy controls; CH, chronic hepatitis; LC, liver cirrhosis; HCC, hepatocellular carcinoma. *P < 0.05; **P < 0.01; ***P < 0.001; P > 0.05 means no significance (NS).

  • Figure 2
    Figure 2

    The receiver operating characteristic curve of AFP (A), AFU (B), GPC3 (C), GGT-II (D), HGF (E), AFP + AFU + GGT-II + GPC3 + HGF (F), AFP + AFU + GPC3 + HGF (G), AFP + AFU + HGF (H), and AFP + AFU (I) in the detection of the NBNC-HCC test group. The sensitivity and specificity represented by the red dots are shown in detail (lower). (A). AFP sensitivity: 59.3% and specificity: 98.9%; (B). AFU sensitivity: 85.2% and specificity: 98.9%; (C). GPC3 sensitivity: 100.0% and specificity: 72.6%; (D). GGT-II sensitivity: 92.6% and specificity: 58.3%; (E). HGF sensitivity: 51.9% and specificity: 88.6%; (F). AFP + AFU + GPC3 + GGT-II + HGF sensitivity: 92.6% and specificity: 98.9%; (G). AFP + AFU + GPC3 + HGF sensitivity: 92.6% and specificity: 99.4%; (H). AFP + AFU + HGF sensitivity: 92.6% and specificity: 99.4%; (I). AFP + AFU sensitivity: 92.6% and specificity: 98.9%.

  • Figure 3
    Figure 3

    Diagnostic outcomes and nomograms for the combination of serum AFP and AFU in the diagnosis of NBNC-HCC. (A). Receiver operating characteristic curves (ROCs) for AFU, AFP, or both for all patients with NBNC-HCC vs. HC in the test cohort. (B). ROC curves for AFU, AFP, or both for all patients with NBNC-HCC vs. HC in the validation cohort. (C). Nomogram of the combined AFP/AFU in diagnosing NBNC-HCC.

  • Figure 4
    Figure 4

    The receiver operating characteristic curves of AFP (A), AFU (B), GPC3 (C), GGT-II (D), and HGF (E), AFP + AFU + HGF (F), AFP + AFU (G), AFP + HGF (H), AFU + HGF (I) in the detection of all-stage HBV-HCC and HCV-HCC of the test group. The sensitivity and specificity represented by the red dots are shown in detail (lower). (A). AFP sensitivity: 52.8% and specificity: 93.7%; (B). AFU sensitivity: 71.5% and specificity: 67.1%; (C). GPC3 sensitivity: 91.1% and specificity: 25.9%; (D). GGT-II sensitivity: 73.2% and specificity: 38.5%; (E). HGF sensitivity: 61.8% and specificity: 75.5%; (F). AFP + AFU + HGF sensitivity: 65.9% and specificity: 89.5%; (G). AFP + AFU sensitivity: 69.1% and specificity: 87.4%; (H). AFP + HGF sensitivity: 74.8% and specificity: 79.0%; (I). AFU + HGF sensitivity: 63.4% and specificity: 76.9%.

  • Figure 5
    Figure 5

    The receiver operating characteristic curves of AFP (A), AFU (B), GPC3 (C), GGT-II (D), and HGF (E), AFP + AFU + HGF (F), AFP + AFU (G), AFP + HGF (H), and AFU + HGF (I) in the detection of early-stage HBV-HCC and HCV-HCC of the test group. The sensitivity and specificity represented by the red dots are shown in detail (lower). (A). AFP sensitivity: 44.3% and specificity: 93.7%; (B). AFU sensitivity: 63.9% and specificity: 67.1%; (C). GPC3 sensitivity: 86.9% and specificity: 28.0%; (D). GGT-II sensitivity: 96.7% and specificity: 11.9%; (E). HGF sensitivity: 50.8% and specificity: 75.5%; (F). AFP + AFU + HGF sensitivity: 52.5% and specificity: 90.2%; (G). AFP + AFU sensitivity: 52.5% and specificity: 91.6%; (H). AFP + HGF sensitivity: 50.8% and specificity: 90.9%; (I). AFU + HGF sensitivity: 34.4% and specificity: 93.0%.

  • Figure 6
    Figure 6

    Diagnostic outcomes and nomogram for the combination of serum AFP and AFU of all-stage and early stage hepatitis-related hepatocellular carcinoma (HCC). (A). Receiver operating characteristic curves (ROCs) for AFU, AFP, or both for all patients with all-stage HBV-HCC and HCV-HCC vs. CH and LC in the test cohort. (B). ROC curves for AFU, AFP, or both for all patients with all-stage HBV-HCC and HCV-HCC vs. CH and LC in the validation cohort. (C). ROC curves for AFU, AFP, or both for all patients with early-stage HBV-HCC and HCV-HCC vs. CH and LC in the test cohort. (D). ROC curves for AFU, AFP, or both for all patients with early-stage HBV-HCC and HCV-HCC vs. CH and LC in the validation cohort. (E). Nomogram of the combined AFP/AFU in diagnosing HBV-HCC and HCV-HCC.

Tables

  • Table 1

    Results for the measurement of serum AFU, AFP, or both, in the diagnosis of NBNC-HCC

    TestValidation
    AUC
    (95% CI)    		Sensitivity
    (%)    		Specificity
    (%)    		PPV
    (%)    		NPV
    (%)    		Positive
    LR    		Negative
    LR    		P
    value    		AUC
    (95% CI)    		Sensitivity
    (%)    		Specificity
    (%)    		PPV
    (%)    		NPV
    (%)    		Positive
    LR    		Negative
    LR    		P
    value
    NBNC-HCC vs. HC (results for measurement of AFU, AFP, or both in the diagnosis of NBNC-HCC)
    AFP0.792 (0.729–0.845)59.3%98.9%88.9%94.0%51.850.41<0.0010.707 (0.639–0.769)51.9%97.7%77.8%92.8%22.250.490.002
    AFU0.967 (0.932–0.987)85.2%98.9%92.0%97.7%74.540.15<0.0010.948 (0.907–0.974)74.1%96.5%76.9%96.0%21.230.27<0.001
    AFP + AFU0.986 (0.958–0.997)92.6%98.9%92.6%98.9%81.020.075<0.0010.969 (0.934–0.988)88.9%94.8%72.7%98.2%16.990.12<0.001

    The diagnostic cutoff values of serum AFP and AFU were 43.23 ng/mL and 16.75 mU/mL, respectively.

    • Table 2

      Results for measurement of serum AFU, AFP, or both, in the diagnosis of HBV-HCC and HCV-HCC

      TestValidation
      AUC
      (95% CI)      		Sensitivity
      (%)      		Specificity
      (%)      		PPV
      (%)      		NPV
      (%)      		Positive
      LR      		Negative
      LR      		P
      value      		AUC
      (95% CI)      		Sensitivity
      (%)      		Specificity
      (%)      		PPV
      (%)      		NPV
      (%)      		Positive
      LR      		Negative
      LR      		P
      value
      Hepatitis-HCC vs. CH and LC (results for the measurement of AFU, AFP, or both in diagnosis of hepatitis-HCC)
      AFP0.780 (0.725–0.828)52.8%93.7%87.8%69.8%8.400.50<0.0010.809 (0.755–0.855)62.8%90.2%85.4%72.7%6.410.41<0.001
      AFU0.752 (0.696–0.803)71.5%67.1%65.2%73.3%2.180.42<0.0010.727 (0.668–0.781)69.4%65.4%64.6%70.2%2.000.47<0.001
      AFP + AFU0.835 (0.784–0.877)69.1%87.4%82.5%76.7%5.490.35<0.0010.841 (0.790–0.884)71.9%86.5%82.9%77.2%5.310.32<0.001
      Early hepatitis-HCC vs. CH and LC (results for measurement of AFU, AFP, or both in diagnosis of early hepatitis-HCC)
      AFP0.741 (0.675–0.800)44.3%93.7%75.0%79.8%7.030.59<0.0010.758 (0.693–0.816)52.2%90.2%73.5%78.4%5.330.53<0.001
      AFU0.666 (0.597–0.730)63.9%67.1%45.3%81.4%1.940.54<0.0010.671 (0.602–0.736)56.5%65.4%45.9%74.4%1.630.67<0.001
      AFP + AFU0.776 (0.712–0.831)52.5%91.6%72.7%81.9%6.250.52<0.0010.791 (0.728–0.845)75.4%73.7%59.8%85.2%2.860.33<0.001

      The diagnostic cutoff values of serum AFP and AFU were 42.34 ng/mL and 13.94 mU/mL, respectively.

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