Skip to main content
Top
Published in: Hepatology International 1/2013

Open Access 01-03-2013 | Review Article

Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta-analysis

Authors: Caroline D. M. Witjes, Susanna M. van Aalten, Ewout W. Steyerberg, Gerard J. J. M. Borsboom, Robert A. de Man, Cornelis Verhoef, Jan N. M. IJzermans

Published in: Hepatology International | Issue 1/2013

Login to get access

Abstract

Purpose

Early detection of hepatocellular carcinoma (HCC) is essential for improved prognosis and long-term survival. To date, screening for HCC depends on serological testing (alpha-fetoprotein, AFP) and imaging (ultrasonography), both of which are not highly sensitive. A meta-analysis was performed to discuss recent developments in biomarkers that may be effective in screening for HCC.

Methods

A systematic search of PubMed, Embase, and Web of Science was performed for articles published between January 2005 and October 2010, and focusing on biomarkers for HCC in urine, serum, or saliva. Data on sensitivity and specificity of tests were extracted from each included article and displayed with a summary ROC. A meta-analysis was carried out in which the area under the curve for each biomarker was used to compare the accuracy of different tests.

Results

In seven well-defined studies, three biomarkers were identified for potential use, namely, Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA). Comparison with AFP showed that GP73 was superior (p = 0.006; 95 % CL −0.23, −0.12), IL-6 was similar (p = 0.66; 95 % CL −0.31, 0.25), and SCCA was inferior to AFP (p = 0.001; 95 % CL 0.12, 0.23).

Conclusion

GP73 is a valuable serum marker that seems to be superior to AFP and can be useful in the diagnosis and screening of HCC. Although GP73 may improve the detection and treatment of one of the most common malignancies worldwide, additional research is required.
Literature
1.
go back to reference Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020–1022PubMedCrossRef Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020–1022PubMedCrossRef
2.
go back to reference Wilson JMG, Junger G. Principles and practice of screening for disease. Geneva: World Health Organization; 1968 Wilson JMG, Junger G. Principles and practice of screening for disease. Geneva: World Health Organization; 1968
3.
go back to reference Welch HG, Schwartz LM, Woloshin S. Are increasing 5-year survival rates evidence of success against cancer? JAMA 2000;283:2975–2978PubMedCrossRef Welch HG, Schwartz LM, Woloshin S. Are increasing 5-year survival rates evidence of success against cancer? JAMA 2000;283:2975–2978PubMedCrossRef
4.
6.
go back to reference Littenberg B, Moses LE. Estimating diagnostic accuracy from multiple conflicting reports: a new meta-analytic method. Med Decis Mak 1993;13:1313–1321CrossRef Littenberg B, Moses LE. Estimating diagnostic accuracy from multiple conflicting reports: a new meta-analytic method. Med Decis Mak 1993;13:1313–1321CrossRef
7.
go back to reference Marrero JA, Romano PR, Nikolaeva O, et al. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol 2005;43:1007–1012PubMedCrossRef Marrero JA, Romano PR, Nikolaeva O, et al. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol 2005;43:1007–1012PubMedCrossRef
8.
go back to reference Mao Y, Yang H, Xu H, et al. Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut 2010;59:1687–1693PubMedCrossRef Mao Y, Yang H, Xu H, et al. Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut 2010;59:1687–1693PubMedCrossRef
9.
go back to reference Porta C, De Amici M, Quaglini S, et al. Circulating interleukin-6 as a tumor marker for hepatocellular carcinoma. Ann Oncol 2008;19:353–358PubMedCrossRef Porta C, De Amici M, Quaglini S, et al. Circulating interleukin-6 as a tumor marker for hepatocellular carcinoma. Ann Oncol 2008;19:353–358PubMedCrossRef
10.
go back to reference Hsia CY, Huo TI, Chiang SY, et al. Evaluation of interleukin-6, interleukin-10 and human hepatocyte growth factor as tumor markers for hepatocellular carcinoma. Eur J Surg Oncol 2007;33:208–212PubMedCrossRef Hsia CY, Huo TI, Chiang SY, et al. Evaluation of interleukin-6, interleukin-10 and human hepatocyte growth factor as tumor markers for hepatocellular carcinoma. Eur J Surg Oncol 2007;33:208–212PubMedCrossRef
11.
go back to reference Giannelli G, Marinosci F, Trerotoli P, et al. SCCA antigen combined with alpha-fetoprotein as serologic markers of HCC. Int J Cancer 2005;117:506–509PubMedCrossRef Giannelli G, Marinosci F, Trerotoli P, et al. SCCA antigen combined with alpha-fetoprotein as serologic markers of HCC. Int J Cancer 2005;117:506–509PubMedCrossRef
12.
go back to reference Giannelli G, Fransvea E, Trerotoli P, et al. Clinical validation of combined serological biomarkers for improved hepatocellular carcinoma diagnosis in 961 patients. Clin Chim 2007;383:147–152CrossRef Giannelli G, Fransvea E, Trerotoli P, et al. Clinical validation of combined serological biomarkers for improved hepatocellular carcinoma diagnosis in 961 patients. Clin Chim 2007;383:147–152CrossRef
13.
go back to reference Hussein MM, Ibrahim AA, Abdella HM, et al. Evaluation of serum squamous cell carcinoma antigen as a novel biomarker for diagnosis of hepatocellular carcinoma in Egyptian patients. Indian J Cancer 2008;45:167–172PubMedCrossRef Hussein MM, Ibrahim AA, Abdella HM, et al. Evaluation of serum squamous cell carcinoma antigen as a novel biomarker for diagnosis of hepatocellular carcinoma in Egyptian patients. Indian J Cancer 2008;45:167–172PubMedCrossRef
14.
go back to reference Gomaa AI, Khan SA, Leen ELS, et al. Diagnosis of hepatocellular carcinoma. World J Gastroenterol 2009;15:1301–1314PubMedCrossRef Gomaa AI, Khan SA, Leen ELS, et al. Diagnosis of hepatocellular carcinoma. World J Gastroenterol 2009;15:1301–1314PubMedCrossRef
15.
go back to reference Shang S, Plymoth A, Ge S, et al. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology 2012;55:483–490PubMedCrossRef Shang S, Plymoth A, Ge S, et al. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology 2012;55:483–490PubMedCrossRef
Metadata
Title
Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta-analysis
Authors
Caroline D. M. Witjes
Susanna M. van Aalten
Ewout W. Steyerberg
Gerard J. J. M. Borsboom
Robert A. de Man
Cornelis Verhoef
Jan N. M. IJzermans
Publication date
01-03-2013
Publisher
Springer-Verlag
Published in
Hepatology International / Issue 1/2013
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-012-9374-3

Other articles of this Issue 1/2013

Hepatology International 1/2013 Go to the issue