DOI QR코드

DOI QR Code

Prognostic Value of Serum AFP, AFP-L3, and GP73 in Monitoring Short-term Treatment Response and Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation

  • Wang, Nan-Ya (Department of Cancer Center, First Hospital of Jilin University) ;
  • Wang, Cong (Department of Cancer Center, First Hospital of Jilin University) ;
  • Li, Wei (Department of Cancer Center, First Hospital of Jilin University) ;
  • Wang, Guan-Jun (Department of Cancer Center, First Hospital of Jilin University) ;
  • Cui, Guo-Zhen (Department of Cancer Center, First Hospital of Jilin University) ;
  • He, Hua (Department of Cancer Center, First Hospital of Jilin University) ;
  • Zhao, Heng-Jun (Department of Cancer Center, First Hospital of Jilin University)
  • Published : 2014.02.28

Abstract

Purpose: Alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and Golgi protein 73 (GP73) levels have been widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to investigate whether these tumor markers could be used to monitor short-term treatment response and recurrence of HCC in patients undergoing radiofrequency ablation (RFA). Methods: Between July 2012 and July 2013, 53 consecutive patients with newly diagnosed HCC were prospectively enrolled in this study. Among these, 32 patients underwent RFA, after which they were followed up prospectively at the First Hospital of Jilin University in China. Results: AFP, AFP-L3, and GP-73 values pre-RFA were not associated with tumor size, whereas AFP and GP-73 levels tended to be associated with tumor number, the presence of vascular invasion, deterioration of liver function, advanced-stage disease, and a poor performance status. GP-73 levels were dramatically elevated in the patients with hepatitis C-associated HCC. Neither pre-RFA nor 1-month post-RFA tumor marker values were associated with short-term outcome. The short-term recurrence rate of AFP-positive patients measured 1 month post-RFA was obviously higher than that of AFP-negative patients. Conclusions: AFP and GP-73 values were associated with clinical variables representing tumor growth and invasiveness, and the AFP value measured 1 month post-RFA was a strong predictor of short-term recurrence in patients with HCC.

Keywords

AFP;AFP-L3;GP-73;hepatocellular carcinoma;radiofrequency ablation

References

  1. Toyoda H, Kumada T, Tada T, et al (2011). Clinical utility of highly sensitive Lens culinaris agglutinin-reactive alphafetoprotein in hepatocellular carcinoma patients with alphafetoprotein <20 ng/mL. Cancer Sci, 102, 1025-31. https://doi.org/10.1111/j.1349-7006.2011.01875.x
  2. Witjes CD, van Aalten SM, Steyerberg EW, et al (2013). Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta-analysis. Hepa Inter, 7, 59-64. https://doi.org/10.1007/s12072-012-9374-3
  3. Yamamoto K, Imamura H, Matsuyama Y, et al (2009). Significance of alpha-fetoprotein and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma undergoing hepatectomy. Ann Surg Oncol, 16, 2795-2804. https://doi.org/10.1245/s10434-009-0618-y
  4. Yamamoto K, Imamura H, Matsuyama Y, et al (2010). AFP, AFP-L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC. J Gastroenterol, 45, 1272-82. https://doi.org/10.1007/s00535-010-0278-5
  5. Yamashita T, Forgues M, Wang W, et al (2008). EpCAM and $\alpha$-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res, 68, 1451-61. https://doi.org/10.1158/0008-5472.CAN-07-6013
  6. Yoshida S, Kurokohchi K, Arima K, et al (2002). Clinical significance of lens culinaris agglutinin-reactive fraction of serum alpha-fetoprotein in patients with hepatocellular carcinoma. Int J Oncol, 20, 305-9.
  7. Sterling RK, Wright EC, Morgan TR, et al (2012). Frequency of Elevated Hepatocellular Carcinoma (HCC). Biomarkers in Patients With Advanced Hepatitis C. Am J Gastroenterol, 107, 64-74. https://doi.org/10.1038/ajg.2011.312
  8. Saito Y, Shimada M, Utsunomiya T, et al (2012). Prediction of recurrence of hepatocellular carcinoma after curative hepatectomy using preoperative Lens culinaris agglutininreactive fraction of alpha-fetoprotein. Hepatol Res, 42, 887-94. https://doi.org/10.1111/j.1872-034X.2012.01004.x
  9. Schutte K, Bornschein J, Malfertheiner P (2009). Hepatocellular carcinoma-epidemiological trends and risk factors. Digest Dis, 27, 80-92.
  10. Shariff MI, Cox IJ, Gomaa AI, et al (2009). Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroent, 3, 353-67. https://doi.org/10.1586/egh.09.35
  11. Taketa K, Sekiya C, Namiki M, et al (1990). Lectin-reactive profiles of alpha-fetoprotein characterizing hepatocellular carcinoma and related conditions. Gastroenterology, 99, 508-18. https://doi.org/10.1016/0016-5085(90)91034-4
  12. Tamura Y, Suda T, Arii S, et al (2013). Value of highly sensitive fucosylated fraction of alpha-fetoprotein for prediction of hepatocellular carcinoma recurrence after curative treatment. Dig Dis Sci, 58, 2406-12. https://doi.org/10.1007/s10620-013-2661-6
  13. Tangkijvanich P, Anukulkarnkusol N, Suwangool P, et al (2000). Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol, 31, 302-08. https://doi.org/10.1097/00004836-200012000-00007
  14. Tateishi R, Shiina S, Yoshida H, et al (2006). Prediction of recurrence of hepatocellular carcinoma after curative ablation using three tumor markers. Hepatology, 44, 1518-27. https://doi.org/10.1002/hep.21408
  15. Toyoda H, Kumada T, Kaneoka Y, et al (2008). Prognostic value of pretreatment levels of tumor markers for hepatocellular carcinoma on survival after curative treatment of patients with HCC. J Hepatol, 49, 223-32. https://doi.org/10.1016/j.jhep.2008.04.013
  16. Llovet JM, Di Bisceglie AM, Bruix J, et al (2008). Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst, 100, 698-711. https://doi.org/10.1093/jnci/djn134
  17. Hu JS, Wu DW, Liang S, Miao XY (2010). GP73, a resident Golgi glycoprotein, is sensibility and specificity for hepatocellular carcinoma of diagnosis in a hepatitis B-endemic Asian population. Med Oncol, 27, 339-45. https://doi.org/10.1007/s12032-009-9215-y
  18. Ioannou GN, Perkins JD, Carithers RL, (2008). Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival. Gastroenterology, 134, 1342-51. https://doi.org/10.1053/j.gastro.2008.02.013
  19. Llovet JM, Bruix J (2000). Early diagnosis and treatment of hepatocellular carcinoma. Best Pract Res Cl Ga, 14, 991-1008. https://doi.org/10.1053/bega.2000.0143
  20. Mao Y, Yang H, Xu H, et al (2010). Golgi protein 73 (GOLPH2). is a valuable serum marker for hepatocellular carcinoma. Gut, 59, 1687-93. https://doi.org/10.1136/gut.2010.214916
  21. Marrero JA, Romano PR, Nikolaeva O, et al (2005). GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol, 43, 1007-12. https://doi.org/10.1016/j.jhep.2005.05.028
  22. Nouso K, Kobayashi Y, Nakamura S, et al (2011). Prognostic importance of fucosylated alpha-fetoprotein in hepatocellular carcinoma patients with low alpha-fetoprotein. J Gastroen Hepatol, 26, 1195-1200. https://doi.org/10.1111/j.1440-1746.2011.06720.x
  23. Oka H, Saito A, Ito K, et al (2001). Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutininreactive alpha-fetoprotein. J Gastroen Hepatol, 16, 1378-83 https://doi.org/10.1046/j.1440-1746.2001.02643.x
  24. Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA-Cancer J Clin, 55, 74-108. https://doi.org/10.3322/canjclin.55.2.74
  25. Riener MO, Stenner F, Liewen H, et al (2009). Golgi phosphoprotein 2 (GOLPH2). expression in liver tumors and its value as a serum marker in hepatocellular carcinomas. Hepatology, 49, 1602-09. https://doi.org/10.1002/hep.22843
  26. Durazo FA, Blatt LM, Corey WG,, et al (2008). Des-gammacarboxyprothrombin, alpha-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma. J Gastroen Hepatol, 23, 1541-8. https://doi.org/10.1111/j.1440-1746.2008.05395.x
  27. Carr BI, Kanke F, Wise M, Satomura S (2007). Clinical evaluation of lens culinaris agglutinin-reactive alphafetoprotein and des-gamma-carboxy prothrombin in histologically proven hepatocellular carcinoma in the United States. Dig Dis Sci, 52, 776-82. https://doi.org/10.1007/s10620-006-9541-2
  28. Chong RJ, Abdullah MS, Hossain MM, Telisinghe PU, Chong VH (2013). Rising incidence of primary liver cancer in Brunei Darussalam. Asian Pac J Cancer Prev, 14, 3473-7. https://doi.org/10.7314/APJCP.2013.14.6.3473
  29. Dai X, Zhao HQ, Liu RH, et al (2012). Percutaneous radiofrequency ablation guided by contrast-enhanced ultrasound in treatment of metastatic hepatocellular carcinoma after liver transplantation. Asian Pac J Cancer Prev, 13, 3709-12. https://doi.org/10.7314/APJCP.2012.13.8.3709
  30. El-Serag HB, Rudolph KL (2007). Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 132, 2557-76. https://doi.org/10.1053/j.gastro.2007.04.061
  31. European Association for the Study of the L, European Organisation for R, Treatment of C (2012). EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol, 56, 908-43. https://doi.org/10.1016/j.jhep.2011.12.001
  32. Fujioka M, Nakashima Y, Nakashima O, Kojiro M (2001). Immunohistologic study on the expressions of alphafetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinoma. Hepatology, 34, 1128-34. https://doi.org/10.1053/jhep.2001.29202
  33. Fujiyama S, Tanaka M, Maeda S, et al (2002). Tumor markers in early diagnosis, follow-up and management of patients with hepatocellular carcinoma. Oncology, 62, 57-63. https://doi.org/10.1159/000048277
  34. Garcia M, Ward E, Center M, et al (2007). Global cancer facts & figures 2007. Atlanta, GA: American Cancer Society
  35. Abdelgawad IA, Mossallam GI, Radwan NH, Elzawahry HM, Elhifnawy NM (2013). Can glypican3 be diagnostic for early hepatocellular carcinoma among Egyptian patients? Asian Pac J Cancer Prev, 14, 7345-9. https://doi.org/10.7314/APJCP.2013.14.12.7345
  36. Bertino G, Ardiri AM, Santonocito MM, Boemi PM (2009). Some patients with HCC haven't abnornormal desgamma- carboxy prothrombin and alpha-fetoprotein levels. Panminerva Medica, 51, 133-4.
  37. Block TM, Comunale MA, Lowman M, et al (2005). Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans. PNAS, 102, 779-84. https://doi.org/10.1073/pnas.0408928102
  38. Bosetti C, Levi F, Boffetta P, et al (2008). Trends in mortality from hepatocellular carcinoma in Europe, 1980-2004. Hepatology, 48, 137-45. https://doi.org/10.1002/hep.22312

Cited by

  1. Clinical Significance of Joint Detection of Serum VEGF, SIL-2R and HGF in Patients with Primary Hepatocellular Carcinoma before and after Percutaneous Microwave Coagulation Therapy vol.15, pp.11, 2014, https://doi.org/10.7314/APJCP.2014.15.11.4545
  2. Differential Expression of IQGAP1/2 in Hepatocellular Carcinoma and its Relationship with Clinical Outcomes vol.15, pp.12, 2014, https://doi.org/10.7314/APJCP.2014.15.12.4951
  3. Elevated PIVKA-II is Associated with Early Recurrence and Poor Prognosis in BCLC 0-A Hepatocellular Carcinomas vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6673
  4. Diagnostic value of alpha-fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels vol.35, pp.12, 2014, https://doi.org/10.1007/s13277-014-2506-8
  5. Abnormal Expression of Golgi Protein 73 in Clinical Values and Their Role in HBV-Related Hepatocellular Carcinoma Diagnosis and Prognosis vol.15, pp.12, 2015, https://doi.org/10.5812/hepatmon.32918
  6. Estimation of Leucine Aminopeptidase and 5-Nucleotidase Increases Alpha-Fetoprotein Sensitivity in Human Hepatocellular Carcinoma Cases vol.16, pp.3, 2015, https://doi.org/10.7314/APJCP.2015.16.3.959
  7. Preparation and Characterization of Anti-GP73 Monoclonal Antibodies and Development of Double-antibody Sandwich ELISA vol.16, pp.5, 2015, https://doi.org/10.7314/APJCP.2015.16.5.2043
  8. Hepatocellular carcinoma: A comprehensive review vol.7, pp.26, 2015, https://doi.org/10.4254/wjh.v7.i26.2648
  9. Overexpression of CD147 is associated with poor prognosis, tumor cell migration and ERK signaling pathway activation in hepatocellular carcinoma vol.14, pp.3, 2017, https://doi.org/10.3892/etm.2017.4818
  10. A sensitive three monoclonal antibodies based automatic latex particle-enhanced turbidimetric immunoassay for Golgi protein 73 detection vol.7, pp.1, 2017, https://doi.org/10.1038/srep40090
  11. Golgi protein 73 and its diagnostic value in liver diseases pp.09607722, 2018, https://doi.org/10.1111/cpr.12538
  12. Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study vol.119, pp.1, 2018, https://doi.org/10.1038/s41416-018-0103-0