中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 3
Mar.  2023
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Article Contents

Value of a scoring system based on the serum levels of alpha-fetoprotein and alkaline phosphatase in predicting the prognosis of patients with resectable hepatocellular carcinoma

DOI: 10.3969/j.issn.1001-5256.2023.03.017
Research funding:

Tianjin Science and Technology Plan Project (19ZXDBSY00010);

Baoding Science and Technology Plan Project (2241ZF219)

More Information
  • Corresponding author: ZHANG Yamin, 13802122219@163.com (ORCID: 0000-0002-3724-6907)
  • Received Date: 2022-08-02
  • Accepted Date: 2022-09-12
  • Published Date: 2023-03-20
  •   Objective  To establish a scoring system based on the preoperative serum levels of alpha-fetoprotein (AFP) and alkaline phosphatase (ALP), and to investigate its value in predicting the prognosis of patients with resectable hepatocellular carcinoma (HCC).  Methods  A retrospective analysis was performed for 154 HCC patients who underwent hepatectomy as the initial treatment in Tianjin First Central Hospital from January 2016 to August 2019. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off values of serum AFP and ALP; the Kaplan-Meier curve and the log-rank test were used for survival analysis to evaluate the relationship between the AFP-ALP score and disease-free survival (DFS); univariate and multivariate Cox regression analyses were used to identify the independent prognostic factors for HCC patients. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups.  Results  The ROC curve analysis showed that serum AFP had an optimal cut-off value of 250.0 ng/mL and an area under the ROC curve (AUC) of 0.674 (95% confidence interval [CI]: 0.580-0.767) in predicting DFS, while serum ALP had an optimal cut-off value of 95.5 U/L and an AUC of 0.745 (95% CI: 0.652-0.838). The survival analysis showed that high preoperative serum levels of AFP (≥250.0 ng/mL) and ALP (≥95.5 U/L) were significantly associated with the poor prognosis of HCC patients (P < 0.001). Based on the AFP-ALP score, all HCC patients were further divided into 0-point group (AFP < 250.0 ng/mL and ALP < 95.5 U/L), 1-point group (AFP≥250.0 ng/mL, ALP < 95.5 U/L; or AFP < 250.0 ng/mL, ALP ≥95.5 U/L), and 2-point group (AFP≥250.0 ng/mL and ALP≥95.5 U/L). The survival curves showed that the 0-, 1-, and 2-point groups had a median DFS of 60.0 (56.7-67.3) months, 20.0 (1.4-36.6) months, and 13.0(7.9-18.0) months, respectively, and there were significant survival differences between the three groups (P < 0.05). Serum AFP-ALP score (1 point vs 0 point: hazard ratio [HR]=4.060, 95% confidence interval [CI]: 2.050-8.039, P < 0.001; 2 points vs 0 point: HR=4.583, 95%CI: 2.385-8.805, P < 0.001) was an independent prognostic factor for HCC patients.  Conclusion  The scoring system based on the serum levels of AFP and ALP can effectively identify HCC patients with poor prognosis, and therefore, it might be used as a simple and reliable tool for prognostic assessment in the clinical treatment of HCC.

     

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  • [1]
    SUNG H, FERLAY J, SIEGEL RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
    [2]
    SIEGEL RL, MILLER KD, FUCHS HE, et al. Cancer statistics, 2021[J]. CA Cancer J Clin, 2021, 71(1): 7-33. DOI: 10.3322/caac.21654.
    [3]
    FORNER A, REIG M, BRUIX J. Hepatocellular carcinoma[J]. Lancet, 2018, 391(10127): 1301-1314. DOI: 10.1016/S0140-6736(18)30010-2.
    [4]
    YANG JD, HAINAUT P, GORES GJ, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(10): 589-604. DOI: 10.1038/s41575-019-0186-y.
    [5]
    European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma[J]. J Hepatol, 2018, 69(1): 182-236. DOI: 10.1016/j.jhep.2018.03.019.
    [6]
    HEINRICH S, SPRINZL M, SCHMIDTMANN I, et al. Validation of prognostic accuracy of MESH, HKLC, and BCLC classifications in a large German cohort of hepatocellular carcinoma patients[J]. United European Gastroenterol J, 2020, 8(4): 444-452. DOI: 10.1177/2050640620904524.
    [7]
    XIANG YJ, WANG K, ZHENG YT, et al. Prognostic value of microvascular invasion in eight existing staging systems for hepatocellular carcinoma: A Bi-Centeric retrospective cohort study[J]. Front Oncol, 2021, 11: 726569. DOI: 10.3389/fonc.2021.726569.
    [8]
    YANG A, XIAO W, CHEN D, et al. The power of tumor sizes in predicting the survival of solitary hepatocellular carcinoma patients[J]. Cancer Med, 2018, 7(12): 6040-6050. DOI: 10.1002/cam4.1873.
    [9]
    LIANG L, WANG MD, ZHANG YM, et al. Association of postoperative biomarker response with recurrence and survival in patients with hepatocellular carcinoma and high alpha-fetoprotein expressions (> 400 ng/ml)[J]. J Hepatocell Carcinoma, 2021, 8: 103-118. DOI: 10.2147/JHC.S289840.
    [10]
    ZHENG Y, ZHU M, LI M. Effects of alpha-fetoprotein on the occurrence and progression of hepatocellular carcinoma[J]. J Cancer Res Clin Oncol, 2020, 146(10): 2439-2446. DOI: 10.1007/s00432-020-03331-6.
    [11]
    HANIF H, ALI MJ, SUSHEELA AT, et al. Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma[J]. World J Gastroenterol, 2022, 28(2): 216-229. DOI: 10.3748/wjg.v28.i2.216.
    [12]
    GALLE PR, FOERSTER F, KUDO M, et al. Biology and significance of alpha-fetoprotein in hepatocellular carcinoma[J]. Liver Int, 2019, 39(12): 2214-2229. DOI: 10.1111/liv.14223.
    [13]
    SUN LY, CEN WJ, TANG WT, et al. Alpha-fetoprotein ratio predicts alpha-fetoprotein positive hepatocellular cancer patient prognosis after hepatectomy[J]. Dis Markers, 2022, 2022: 7640560. DOI: 10.1155/2022/7640560.
    [14]
    SHE WH, CHAN MY, MA KW, et al. Alpha-fetoprotein in predicting survival of patients with ruptured hepatocellular carcinoma after resection[J]. J Invest Surg, 2022, 35(5): 1091-1097. DOI: 10.1080/08941939.2021.2012615.
    [15]
    TSILIMIGRAS DI, MORIS D, HYER JM, et al. Serum α-fetoprotein levels at time of recurrence predict post-recurrence outcomes following resection of hepatocellular carcinoma[J]. Ann Surg Oncol, 2021, 28(12): 7673-7683. DOI: 10.1245/s10434-021-09977-x.
    [16]
    HEINRICH D, BRULAND Ø, GUISE TA, et al. Alkaline phosphatase in metastatic castration-resistant prostate cancer: reassessment of an older biomarker[J]. Future Oncol, 2018, 14(24): 2543-2556. DOI: 10.2217/fon-2018-0087.
    [17]
    CAI X, CHEN Z, CHEN J, et al. Albumin-to-alkaline phosphatase ratio as an independent prognostic factor for overall survival of advanced hepatocellular carcinoma patients without receiving standard anti-cancer therapies[J]. J Cancer, 2018, 9(1): 189-197. DOI: 10.7150/jca.21799.
    [18]
    SUN P, CHEN S, LI Y. The association between pretreatment serum alkaline phosphatase and prognosis in hepatocellular carcinoma: A meta-analysis[J]. Medicine (Baltimore), 2020, 99(11): e19438. DOI: 10.1097/MD.0000000000019438.
    [19]
    WU SJ, LIN YX, YE H, et al. Prognostic value of alkaline phosphatase, gamma-glutamyl transpeptidase and lactate dehydrogenase in hepatocellular carcinoma patients treated with liver resection[J]. Int J Surg, 2016, 36(Pt A): 143-151. DOI: 10.1016/j.ijsu.2016.10.033.
    [20]
    PIRAS-STRAUB K, KHAIRZADA K, GERKEN G, et al. Glutamate dehydrogenase and alkaline phosphatase as very early predictors of hepatocellular carcinoma recurrence after liver transplantation[J]. Digestion, 2015, 91(2): 117-127. DOI: 10.1159/000370212.
    [21]
    XIA F, NDHLOVU E, LIU Z, et al. Alpha-fetoprotein+alkaline phosphatase (A-A) score can predict the prognosis of patients with ruptured hepatocellular carcinoma underwent hepatectomy[J]. Dis Markers, 2022, 2022: 9934189. DOI: 10.1155/2022/9934189.
    [22]
    HU X, CHEN R, WEI Q, et al. The landscape of alpha fetoprotein in hepatocellular carcinoma: where are we?[J]. Int J Biol Sci, 2022, 18(2): 536-551. DOI: 10.7150/ijbs.64537.
    [23]
    YANG SL, LIU LP, YANG S, et al. Preoperative serum α-fetoprotein and prognosis after hepatectomy for hepatocellular carcinoma[J]. Br J Surg, 2016, 103(6): 716-724. DOI: 10.1002/bjs.10093.
    [24]
    TSILIMIGRAS DI, HYER JM, DIAZ A, et al. Synergistic impact of alpha-fetoprotein and tumor burden on long-term outcomes following curative-intent resection of hepatocellular carcinoma[J]. Cancers (Basel), 2021, 13(4): 747. DOI: 10.3390/cancers13040747.
    [25]
    PAN YX, SUN XQ, HU ZL, et al. Prognostic values of alpha-fetoprotein and des-gamma-carboxyprothrombin in hepatocellular carcinoma in china: an analysis of 4792 patients[J]. J Hepatocell Carcinoma, 2021, 8: 657-670. DOI: 10.2147/JHC.S316223.
    [26]
    SHARMA U, PAL D, PRASAD R. Alkaline phosphatase: an overview[J]. Indian J Clin Biochem, 2014, 29(3): 269-278. DOI: 10.1007/s12291-013-0408-y.
    [27]
    YAMAMOTO K, AWOGI T, OKUYAMA K, et al. Nuclear localization of alkaline phosphatase in cultured human cancer cells[J]. Med Electron Microsc, 2003, 36(1): 47-51. DOI: 10.1007/s007950300006.
    [28]
    YU MC, CHAN KM, LEE CF, et al. Alkaline phosphatase: does it have a role in predicting hepatocellular carcinoma recurrence?[J]. J Gastrointest Surg, 2011, 15(8): 1440-1449. DOI: 10.1007/s11605-011-1537-3.
    [29]
    HUANG CW, WU TH, HSU HY, et al. Reappraisal of the role of alkaline phosphatase in hepatocellular carcinoma[J]. J Pers Med, 2022, 12(4): 518. DOI: 10.3390/jpm12040518.
    [30]
    CHICCO D, ONETO L. Computational intelligence identifies alkaline phosphatase (ALP), alpha-fetoprotein (AFP), and hemoglobin levels as most predictive survival factors for hepatocellular carcinoma[J]. Health Informatics J, 2021, 27(1): 1460458220984205. DOI: 10.1177/1460458220984205.
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