Significance of Glypican-3 in Early Detection of Hepatocellular Carcinoma in Cirrhotic Patients
Egypt has high incidence of hepatocellular carcinoma (HCC). This is due to wide spread of hepatitis C virus (HCV) infection which is responsible for most of the cases of liver cirrhosis. The major diagnostic techniques for HCC include serum markers and various imaging modalities. Glypican 3 (GPC3) protein is highly expressed in HCC, but not in normal liver tissue. The significance of GPC3 as a predictor or diagnostic tool for human tumors other than HCC is unclear.
To quantitatively assess the role of GPC3 in diagnosis of HCC in comparison to α-fetoprotein (AFP), ultrasonography (US), and computerized tomography (CT).
Patients and Methods
This cross-sectional study enrolled 85 subjects: 40 cirrhotic patients with primary HCC, 30 cirrhotic patients without HCC, and 15 healthy individuals. All patients were recruited from the Gastroenterology and Tropical Departments and outpatient clinics of New Damietta Hospital during the period from November 2010 to August 2012.
GPC3 is positive in some HCC patients with normal levels of AFP. AFP has lower sensitivity (67.5%) compared to higher sensitivity of GPC3 (82.5%), and near specificity (61.2%) to GPC3 (57.8%).
Conclusion and Significance
The combined serum AFP and GPC3 significantly increased the sensitivity of HCC diagnosis. Although GPC3 is better than AFP in diagnosis of HCC, it still lacks the 100% sensitivity and specificity because some patients have negative or normal level of GPC3 (below the cutoff point 1.5 ng/ml) despite being diagnosed by triphasic CT.
Keywordsα-Fetoprotein Ultrasonography Triphasic CT Glypican-3 Hepatocellular carcinoma Cirrhosis Viral hepatitis
All authors contributed to conception, design, data analysis, and writing the manuscript. D.J. provided ENDNOTE X8 software required for the production of this manuscript.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the research committees of Al-Azher University Faculty of Medicine and Al-Azhar University Hospital in New Damietta, Egypt.
Written consent was obtained from all individual participants.
- 8.Hameed MA, Waqas S. Physiological basis and clinical utility of erythrocyte sedimentation rate. Continuing Med Educ. 2006;22(2)Google Scholar
- 10.Lewis S, Barbara B, Imelda B. Dacie and Lewis Practical Haematology, 10th Edition. Churchill Livingstone. 2006.Google Scholar
- 11.Grant GH, Kachmar JF. Fundamentals of clinical chemistry. Tietz NW, ed. W.B. Philadelphia: Sunders Co; 1976.Google Scholar
- 14.Tietz NW, editor. Clinical guide to laboratory tests. 3rd ed. Philadelphia: W.B. Saunders; 1995.Google Scholar
- 16.Taylor EH. Clin Chem. 1989;4:58–62.Google Scholar
- 18.Lerner KK, Lerner BW. World of microbiology and immunology. Volumes 1 and 2. Andover: Cengage Gale Publisher; 2003. p. 231–232.Google Scholar
- 20.Gurakar A, Hamilton J, Koteish A. Diagnosis of hepatocellular carcinoma. World J Gastroenterol. 2011;14(13):1461.Google Scholar
- 29.Rodriguez-Diaz JL, Rosas-Camargo V, Vega-Vega O, Morales-Espinosa D, Mendez-Reguera A, Martinez-Tlahuel JL, et al. Clinical and pathological factors associated with the development of hepatocellular carcinoma in patients with hepatitis virus-related cirrhosis: a long-term follow-up study. Clin Oncol (R Coll Radiol). 2007;19(3):197–203.CrossRefGoogle Scholar
- 30.Johnson P. Malignant tumors of the liver. In: O’Grady J, Lake J, editors. “Comprehensive Clinical Hepatology”. London: Haecourt; 2000. p. 25.1–25.18.Google Scholar
- 34.Abdel-Wahab M, El-Ghawalby N, Mostafa M, Sultan A, El-Sadany M, Fathy O, et al. Epidemiology of hepatocellular carcinoma in lower Egypt, Mansoura Gastroenterology Center. Hepato-Gastroenterology. 2006;54(73):157–62.Google Scholar
- 37.Chritsopher J, Smith M. Clinician guide to viral hepatitis. Hepatol Res. 2004;32:245–61.Google Scholar
- 43.Chen T, Huang P, Tsai M, Lin L, Liu C, Ho K, et al. Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a–ribavirin combination therapy. J Gastroenterol Hepatol. 2007;22(5):669–75.CrossRefPubMedGoogle Scholar
- 44.Shirabe K, Itoh S, Yoshizumi T, Soejima Y, Taketomi A, Aishima S, et al. The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma-with special reference to the serum levels of des-gamma-carboxy prothrombin. J Surg Oncol. 2007;95(3):235–40.CrossRefPubMedGoogle Scholar