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GPC-HCC model: a combination of glybican-3 with other routine parameters improves the diagnostic efficacy in hepatocellular carcinoma

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Tumor Biology

Abstract

Conflicting results for circulating glypican-3 (GPC3) were reported in hepatocellular carcinoma (HCC) diagnosis. We aimed to improve the diagnostic power of GPC3 by developing a GPC-HCC model for diagnosing HCC. GPC3 was tested for HCC (138), liver cirrhosis (56), and fibrosis (62) patients by ELISA. Data from patient groups were retrospectively analyzed. A novel score, GPC-HCC, based on combination of GPC3 and routine laboratory tests, was developed for HCC diagnosis. The GPC-HCC model values produced a significant 1.7-fold increase in liver cirrhosis and 3.2-fold increase in HCC, in comparison with liver fibrosis. In contrast to GPC3 and alpha fetoprotein (AFP), the GPC-HCC model showed high HCC diagnostic power with area under the curve (AUC) of 0.939, sensitivity 93 %, specificity 93 %, positive predictive value 89 %, negative predictive value 95 %, and efficiency 93 %. GPC-HCC AUC in HCC with single tumor, absent vascular invasion, and tumor size ≤3 cm were 0.93, 0.92, and 0.92, respectively, compared with 0.63, 0.63, and 0.64, respectively, for GPC3 and 0.69, 0.70, 0.55, respectively, for AFP. In conclusion, owing to these promising findings, the combination of GPC3 with other laboratory simple routine tests (GPC-HCC model) could improve the diagnostic power of GPC3 in HCC screening and follow up of cirrhotic patients.

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References

  1. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–27.

    Article  CAS  PubMed  Google Scholar 

  2. Kelley RK, Magbanua MJ, Butler TM, et al. Circulating tumor cells in hepatocellular carcinoma: a pilot study of detection, enumeration, and next-generation sequencing in cases and controls. BMC Cancer. 2015;15:206.

    Article  PubMed  PubMed Central  Google Scholar 

  3. El-mezayen HA, Darwish H. Development of a novel score for early detection of hepatocellular carcinoma among high-risk hepatitis C virus patients. Tumour Biol. 2014;35:6501–9.

    Article  CAS  PubMed  Google Scholar 

  4. Shariff MI, Cox IJ, Gomaa AI, et al. Hepato cellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroenterol Hepatol. 2009;3:353–67.

    Article  PubMed  Google Scholar 

  5. Mukozu T, Nagai H, Matsui D, Kanekawa T, Sumino Y. Serum VEGF as a tumor marker in patients with HCV-related liver cirrhosis and hepatocellular carcinoma. Anticancer Res. 2013;33:1013–21.

    PubMed  Google Scholar 

  6. Attallah AM, Omran MM, Attallah AA, et al. HCC-ART score, a simple, highly sensitive and specific test for early diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Br J Cancer. 2013;109:1657–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Filmus J, Shi W, Wong ZM, Wong MJ. Identification of a new membrane-bound heparan sulphate proteoglycan. Biochem J. 1995;311:561–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jia HL, Ye QH, Qin LX, et al. Gene expression profiling reveals potential biomarkers of human hepatocellular carcinoma. Clin Cancer Res. 2007;13:1133–9.

    Article  CAS  PubMed  Google Scholar 

  9. Kandil D, Leiman G, Allegrettaetal M. Glypican-3 immuno-cytochemistry in liver fine-needle aspirates: a novel stain to assist in the differentiation of benign and malignant liver lesions. Cancer. 2007;111:316–22.

    Article  PubMed  Google Scholar 

  10. Capurro M, Wanless IR, Sherman M, et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology. 2003;125:89–97.

    Article  CAS  PubMed  Google Scholar 

  11. Chen M, Li G, Yanetal J. Reevaluation of glypican-3 as a serological marker for hepatocellular carcinoma. Clin Chim Acta. 2013;423:105–11.

    Article  CAS  PubMed  Google Scholar 

  12. Wang Y, Yang H, Xu H, et al. Golgi protein 73, not Glypican-3, may be a tumor marker complementary to α-fetoprotein for hepatocellular carcinoma diagnosis. J Gastroenterol Hepatol. 2014;29:597–602.

    Article  CAS  PubMed  Google Scholar 

  13. Ozkan H, Erdal H, Kocak, et al. Diagnostic and prognostic role of serum glypican 3 in patients with hepatocellular carcinoma. J Clin Lab Anal. 2011;25:350–3.

    Article  PubMed  Google Scholar 

  14. Jia X, Gao Y, Zhai D, et al. Assessment of the clinical utility of glypican 3 as a serum marker for the diagnosis of hepatocellular carcinoma. Technol Cancer Res Treat. 2015. doi:10.1177/1533034615605248.

  15. Perkins NJ, Schisterman EF. The inconsistency of ‘optimal’ cut points obtained using two criteria based on the receiver operating characteristics curve. Am J Epidemiol. 2006;163:670–5.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Zakhary NI, Mohamed MS, Khorshid O, Azer RS, Zayed N. Role of glypican-3 in the early diagnosis of hepatocellular carcinoma among Egyptian patients. J Genet Eng Biotechnol. 2012;10:73–9.

    Article  CAS  Google Scholar 

  17. Gomaa AI, Hendy OM, Abou Raia GY, et al. The diagnostic value of peripheral blood glypican-3 in patients with hepatocellular carcinoma. World J Med Sci. 2012;7:105–12.

  18. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–36.

    Article  PubMed  Google Scholar 

  19. Gish RG. Early detection of hepatocellular carcinoma through surveillance using biomarkers. Gastroenterol Hepatol (N Y). 2014;10:121–3.

    Google Scholar 

  20. Ishizuka M, Kubota K, Kita J, Shimoda M, Kato M, Sawada T. Impact of an inflammation-based prognostic system on patients undergoing surgery for hepatocellular carcinoma: a retrospective study of 398 Japanese patients. Am J Surg. 2012;203:101–6.

    Article  PubMed  Google Scholar 

  21. Attallah AM, El-Far M, Abdel Malak CA, et al. Evaluation of cytokeratin-1 in the diagnosis of hepatocellular carcinoma. Clin Chim Acta. 2011;412:2310–5.

    Article  CAS  PubMed  Google Scholar 

  22. Nakatsura T, Yoshitake Y, Senju S, et al. Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochem Biophys Res Commun. 2003;306:16–25.

    Article  CAS  PubMed  Google Scholar 

  23. Libbrecht L, Severi T, Cassiman D, et al. Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am J Surg Pathol. 2006;30:1405–11.

    Article  PubMed  Google Scholar 

  24. Yang SL, Fang X, Huang ZZ, et al. Can serum glypican-3 be a biomarker for effective diagnosis of hepatocellular carcinoma? A meta-analysis of the literature. Dis Markers. 2014;2014:127831.

    PubMed  PubMed Central  Google Scholar 

  25. Liu H, Li P, Zhai Y, et al. Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma. World J Gastroenterol. 2010;16:4410–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhao YJ, Ju Q, Li GC. Tumor markers for hepatocellular carcinoma. Mol Clin Oncol. 2013;1:593–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Subramaniam S, Kelley RK, Venook AP. A review of hepatocellular carcinoma (HCC) staging systems. Chin Clin Oncol. 2013;2:33.

    PubMed  Google Scholar 

  28. Toyoda H, Kumada T, Osaki Y, et al. Staging hepatocellular carcinoma by a novel scoring system (BALAD score) based on serum markers. Clin Gastroenterol Hepatol. 2006;4:1528–36.

    Article  CAS  PubMed  Google Scholar 

  29. Tateishi R, Yoshida H, Shiina S, et al. Proposal of a new prognostic model for hepatocellular carcinoma: an analysis of 403 patients. Gut. 2005;54:419–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33:550–8.

    Article  PubMed  Google Scholar 

  31. Patel M, Shariff MI, Ladep NG, et al. Hepatocellular carcinoma: diagnostics and screening. J Eval Clin Pract. 2012;18:335–42.

    Article  PubMed  Google Scholar 

  32. Hennedige T, Venkatesh SK. Imaging of hepatocellular carcinoma: diagnosis, staging and treatment monitoring. Cancer Imaging. 2013;12:530–47.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sterling RK, Jeffers L, Gordon F, et al. Utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2009;7:104–13.

    Article  CAS  PubMed  Google Scholar 

  34. Shen Q, Fan J, Yang XR, et al. Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Lancet Oncol. 2012;13:817–26.

    Article  CAS  PubMed  Google Scholar 

  35. Shang S, Plymoth A, Ge S, Feng Z, Rosen HR, Sangrajrang S. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology (Baltimore, MD). 2012;55:483–90.

    Article  CAS  Google Scholar 

  36. Ge T, Shen Q, Wang N, et al. Diagnostic values of alpha-fetoprotein, dickkopf-1, and osteopontin for hepatocellular carcinoma. Med Oncol. 2015;32:59.

    Article  PubMed  Google Scholar 

  37. Tangkijvanich P, Chanmee T, Komtong S, et al. Diagnostic role of serum glypican-3 in differentiating hepatocellular carcinoma from non-malignant chronic liver disease and other liver cancers. J Gastroenterol Hepatol. 2010;25:129–37.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank the staff of the Biotechnology Research Center, New Damietta, Egypt for their assistance in this study. This work has been completely supported financially and carried out at the Biotechnology Research Center, New Damietta, Egypt.

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Authors and Affiliations

  1. Biotechnology Research Center, P.O. Box (14), 23 July St., Industrial Zone, New Damietta, 34517, Egypt

    Abdelfattah M. Attallah, Mohamed A. Abdelrazek, Ahmed A. Attallah & Aya M. Saeed

  2. Faculty of Science, Mansoura University, Mansoura, Egypt

    Mohamed El-Far

  3. Faculty of Science, Helwan University, Cairo, Egypt

    Mohamed M. Omran

  4. Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Khaled Farid

Authors
  1. Abdelfattah M. Attallah
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  2. Mohamed El-Far
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  3. Mohamed M. Omran
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  4. Mohamed A. Abdelrazek
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  5. Ahmed A. Attallah
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  6. Aya M. Saeed
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  7. Khaled Farid
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Correspondence to Abdelfattah M. Attallah.

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The study protocol was approved by the Institutional Review Committee and conformed to the ethical guidelines of the 1975 Helsinki Declaration.

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Attallah, A.M., El-Far, M., Omran, M.M. et al. GPC-HCC model: a combination of glybican-3 with other routine parameters improves the diagnostic efficacy in hepatocellular carcinoma. Tumor Biol. 37, 12571–12577 (2016). https://doi.org/10.1007/s13277-016-5127-6

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  • DOI: https://doi.org/10.1007/s13277-016-5127-6

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