Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Elevated PIVKA-II is Associated with Early Recurrence and Poor Prognosis in BCLC 0-A Hepatocellular Carcinomas

  • Wang, Bei-Li (Department of Laboratory Medicine, Zhongshan Hospital, Fudan University) ;
  • Tan, Qi-Wen (Department of Laboratory Medicine, Zhongshan Hospital, Fudan University) ;
  • Gao, Xing-Hui (Department of Laboratory Medicine, Zhongshan Hospital, Fudan University) ;
  • Wu, Jiong (Department of Laboratory Medicine, Zhongshan Hospital, Fudan University) ;
  • Guo, Wei (Department of Laboratory Medicine, Zhongshan Hospital, Fudan University)
  • Published : 2014.08.30
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Abstract

Background: To investigate the prognostic value of serum PIVKA-II (prothrombin induced by the absence of vitamin K or antagonist-II) in BCLC (Barcelona Clinic Liver Cancer) 0-A hepatocellular carcinoma (HCC) patients after curative resection. Materials and Methods: Preoperative sera were collected from 140 patients with BCLC 0-A HCCs undergoing curative resection during 2011-2012 in Zhongshan Hospital. Follow-up ended on November 2013. ELISA was used to detect the serum concentrations of preoperative PIVKA-II. The prognostic value of PIVKA-II and other clinicopathological factors was analyzed by the Kaplan-Meier method and the multivariate Cox proportional hazards model. Results: During follow-up, 39 of 140 patients suffered recurrence and the 1-year recurrence rate was 27.9%. The high-PIVKA-II expression group had lower 1-year time to progression (TTP) compared with the low-expression group (54.8% vs 20.2%, p<0.001). Patients with high preoperative PIVKA-II expression showed a relatively higher risk of developing postoperative recurrence than those with low expression in the low-recurrence-risk subgroups, including ${\alpha}$-fetoprotein ${\leq}400ng/mL$ (45.4% vs 16.7%; p=0.006), tumor size ${\leq}5cm$ (54.2% vs 18.1%; p<0.001), single tumor (56.0% vs 19.1%; p<0.001), absence of satellite lesions (53.3% vs 19.8%; p=0.001), absence of vascular invasion (52.6% vs 14.9%; p=0.002), and Edmondson stage I/II (60.9% vs 20.3%; p<0.001). PIVKA-II was the strongest independent prognostic factor for TTP (hazard ratio, 2.877; 95% CI 1.524-5.429; p=0.001). Conclusions: Elevated PIVKA-II is associated with early recurrence of BCLC 0-A HCC after curative resection and can be considered a novel prognostic predictor.

Keywords

References

  1. Bertino G, Ardiri A, Malaguarnera M, et al (2012). Hepatocellualar carcinoma serum markers. Semin Oncol, 39, 410-33. https://doi.org/10.1053/j.seminoncol.2012.05.001
  2. Bruix J, Sherman M (2011). Management of hepatocellular carcinoma: an update. Hepatology, 53, 1020-2. https://doi.org/10.1002/hep.24199
  3. Cai XY, Wang JX, Yi Y, et al (2014). Low counts of ${\gamma}{\delta}$ T cells in peritumoral liver tissue are related to more frequent recurrence in patients with hepatocellular carcinoma after curative resection. Asian Pac J Cancer Prev, 15, 775-80. https://doi.org/10.7314/APJCP.2014.15.2.775
  4. Cha C, Fong Y, Jarnagin WR, et al (2003). Predictors and patterns of recurrence after resection of hepatocellular carcinoma. J Am Coll Surg, 197, 753-8. https://doi.org/10.1016/j.jamcollsurg.2003.07.003
  5. Chan SL, Mo FK, Johnson PJ, et al (2009). New utility of an old marker: serial-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy. J Clin Oncol, 27, 446-52.
  6. Gupta SP, Mittal A, Sathian B, et al (2013). Elevated serum insulin is an independent risk factor for hepatocellular carcinoma: a case control study from Nepal. Asian Pac J Cancer Prev, 14, 7331-3. https://doi.org/10.7314/APJCP.2013.14.12.7331
  7. Kang SH, Kim do Y, Jeon SM, et al (2012). Clinical characteristics and prognosis of hepatocellular carcinoma with different sets of serum AFP and PIVKA-II levels. Eur J Gastroenterol Hepatol, 24, 849-56. https://doi.org/10.1097/MEG.0b013e3283535c34
  8. Kim do Y, Paik YH, Ahn SH, et al (2007). PIVKA-II is a useful tumor marker for recurrent hepatocellular carcinoma after surgical resection. Oncology, 72, 52-7. https://doi.org/10.1159/000111707
  9. Kim JM, Hyuck C, Kwon D, et al (2013). Protein induced by vitamin K antagonist-II (PIVKA-II) is a reliable prognostic factor in small hepatocellular carcinoma. World J Surg, 37, 1371-8. https://doi.org/10.1007/s00268-013-1966-0
  10. Li N, Hu WJ, Shi J, et al (2013). Roles of fibroblast growth factor-inducible 14 in hepatocellular carcinoma. Asian Pac J Cancer Prev, 14, 3509-14. https://doi.org/10.7314/APJCP.2013.14.6.3509
  11. Lovet JM, Bru C, Bruix J (1999). Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis, 19, 329-38. https://doi.org/10.1055/s-2007-1007122
  12. Matsubara M, Shiraha H, Kataoka J, et al (2012). Des-$\gamma$-carboxyl prothrombin is associated with tumor angiogenesis in hepatocellular carcinoma. J Gastroenterol Hepatol, 27, 1602-8. https://doi.org/10.1111/j.1440-1746.2012.07173.x
  13. Mittal A, Gupta SP, Sathian B, et al (2012). Des-gammacarboxyprothrombin for early identification and prognosis of hepatocellular carcinoma: a case control study from western Nepal. Asian Pac J Cancer Prev, 13, 5773-5. https://doi.org/10.7314/APJCP.2012.13.11.5773
  14. Park H, Park JY (2013). Clinical significance of AFP and PIVKA-II responses for monitoring treatment outcomes and predicting prognosis in patients with hepatocellular carcinoma. Biomed Res Int, 310427.
  15. Santi V, Trevisani F, Gramenzi A, et al (2010). Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival. J Hepatol, 53, 291-7. https://doi.org/10.1016/j.jhep.2010.03.010
  16. Shah SA, Greig PD, Gallinger S, et al (2006). Factors associated with early recurrence after resection for hepatocellular carcinoma and outcomes. J Am Coll Surg, 202, 275-83. https://doi.org/10.1016/j.jamcollsurg.2005.10.005
  17. Shah SA, Cleary SP, Wei AC, et al (2007). Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery, 141, 330-9. https://doi.org/10.1016/j.surg.2006.06.028
  18. Shi L, Wu LL, Yang JR, et al (2014). Serum peroxiredoxin3 is a useful biomarker for early diagnosis and assessemnt of prognosis of hepatocellular carcinoma in Chinese patients. Asian Pac J Cancer Prev, 15, 2979-86. https://doi.org/10.7314/APJCP.2014.15.7.2979
  19. Siegel R, Naishadham D, Jemal A (2012). Cancer statistics, 2012. CA Cancer J Clin, 62, 10-29. https://doi.org/10.3322/caac.20138
  20. Takayama T, Makuuchi M, Kojiro M, et al (2008). Early hepatocellular carcinoma: pathology, imaging, and therapy. Ann Surg Oncol, 15, 972-8. https://doi.org/10.1245/s10434-007-9685-0
  21. Tung-Ping Poon R, Fan ST, Wong J (2000). Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg, 232, 10-24. https://doi.org/10.1097/00000658-200007000-00003
  22. Wang SB, Cheng YN, Cui SX, et al (2009a). Des-gammacarboxy prothrombin stimulates human vascular endothelial cell growth and migration. Clin Exp Metastasis, 26, 469-77. https://doi.org/10.1007/s10585-009-9246-y
  23. Wang CC, Iyer SG, Low JK, et al (2009b). Perioperative factors affecting long-term outcomes of 473 consecutive patients undergoing hepatectomy for hepatocellular carcinoma. Ann Surg Oncol, 16, 1832-42. https://doi.org/10.1245/s10434-009-0448-y
  24. Wang NY, Wang C, Li W, et al (2014). Prognostic value of serum AFP, AFP-L3, and GP73 in monitoring short-term treatment response and recurrence of hepatocellular carcinoma after radiofrequency ablation. Asian Pac J Cancer Prev, 15, 1539-44. https://doi.org/10.7314/APJCP.2014.15.4.1539
  25. 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

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