Liver Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 21, 2006; 12(47): 7604-7612
Published online Dec 21, 2006. doi: 10.3748/wjg.v12.i47.7604
New multi protein patterns differentiate liver fibrosis stages and hepatocellular carcinoma in chronic hepatitis C serum samples
Thomas Göbel, Sonja Vorderwülbecke, Katarzyna Hauck, Holger Fey, Dieter Häussinger, Andreas Erhardt
Thomas Göbel, Katarzyna Hauck, Holger Fey, Dieter Häussinger, Andreas Erhardt, Klinik für Gastroenterologie, Hepatologie und Infektiologie, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany
Sonja Vorderwülbecke, Ciphergen Biosystems, Neuendorfstr. 24a, D-16761 Hennigsdorf bei Berlin, Germany
Author contributions: All authors contributed equally to the work.
Supported by a research grant of the Jürgen Manchot Stiftung
Correspondence to: Andreas Erhardt, MD, Klinik für Gastroenterologie, Hepatologie und Infektiologie, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany. erhardt@uni-duesseldorf.de
Telephone: +49-211-8118268 Fax: +49-211-8118132
Received: August 5, 2006
Revised: August 15, 2006
Accepted: August 22, 2006
Published online: December 21, 2006
Abstract

AIM: To identify a multi serum protein pattern as well as single protein markers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) for detection and differentiation of liver fibrosis (F1-F2), liver cirrhosis (F4) and hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV).

METHODS: Serum samples of 39 patients with F1/F2 fibrosis, 44 patients with F4 fibrosis, 34 patients with HCC were applied to CM10 arrays and analyzed using the SELDI-TOF ProteinChip System (PBS-IIc; Ciphergen Biosystems) after anion-exchange fractionation. All patients had chronic hepatitis C and histologically confirmed fibrosis stage/HCC. Data were analyzed for protein patterns by multivariate statistical techniques and artificial neural networks.

RESULTS: A 4 peptide/protein multimarker panel (7486, 12 843, 44 293 and 53 598 Da) correctly identified HCCs with a sensitivity of 100% and specificity of 85% in a two way-comparison of HCV-cirrhosis versus HCV-HCC training samples (AUROC 0.943). Sensitivity and specificity for identification of HCC were 68% and 80% for random test samples. Cirrhotic patients could be discriminated against patients with F1 or F2 fibrosis using a 5 peptide/protein multimarker pattern (2873, 6646, 7775, 10 525 and 67 867 Da) with a specificity of 100% and a sensitivity of 85% in training samples (AUROC 0.976) and a sensitivity and specificity of 80% and 67% for random test samples. Combination of the biomarker classifiers with APRI score and alfa-fetopotein (AFP) improved the diagnostic performance. The 6646 Da marker protein for liver fibrosis was identified as apolipoprotein C-I.

CONCLUSION: SELDI-TOF-MS technology combined with protein pattern analysis seems a valuable approach for the identification of liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis C. Most probably a combination of different serum markers will help to identify liver cirrhosis and early-stage hepatocellular carcinomas in the future.

Keywords: Hepatocellular carcinoma, Hepatitis C virus, Apolipoprotein C-I, Proteomics, Surface-enhanced laser desorption/ionisation