gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Identification of the gene coding for the Serine Proteinase Inhibitor kazal-type 1 (SPINK1) as the most uniform overexpressed gene in HCV-induced Hepatocarcinogenesis by genomic profiling using Oligonucleotide-MicroArrays

Meeting Abstract

  • corresponding author presenting/speaker Holger G. Hass - University Medical Center II, South West German Cancer Center, Tuebingen, Tübingen, Deutschland
  • Jürgen Jobst - Fa. Matrigene GmbH, Reutlingen
  • Oliver Nehls - University Medical Center II, South West German Cancer Center, Tuebingen
  • Jörg T. Hartmann - University Medical Center II, South West German Cancer Center, Tuebingen
  • Stephan Kaiser - University Medical Clinic Center I, Tuebingen

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO189

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Hass et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Background: Chronic infection with Hepatitis C (HCV) is one of the major risk factors worldwide for the development of hepatocellular carcinoma (HCC). Several studies suggest an oncogenic potential of HCV, but the molecular pathomechanism leading to HCV-induced hepatocarcinogenesis is still unknown. The aim of this study was to investigate HCV-induced carcinogenesis by analyzing gene expression profiles of HCV positive HCC and comparing them to HCC of other causes using oligonucleotide-microarrays.

Methods: Malignant and non-malignant tissue from 24 patients (8 HCV positive, 6 HBV positive, 10 ethyl-toxic induced HCCs) have been analyzed. After isolation of total RNA and transcription into cDNA, biotin-labelled cRNA probes were hybridized to GeneArrays (Affymetrix U 133A). Expression levels of more than 22.000 probes (genes/ESTs) were determined and 2-dimensional cluster analyses were performed using special software programs (Genexplore©, GeneSpring©).

Results: Using 2-dimensional cluster analysis of the microarray data sets, a fast and safe differentiation between malignant vs. non-malignant liver tissue of all cases was possible. In HCV-induced HCC tissue a constant overexpression (>2.0fold) of 58 genes was found when compared to the corresponding non-malignant liver tissue. In comparison to HCC samples from HCV negative patients a specific overexpression of 11 genes was detected in HCV-induced carcinomas. Interestingly, the gene coding for the serine protein kinase inhibitor 1 (SPINK 1) was one of the most overexpressed genes in HCV positive HCC (range, 2.5-33.5foldchange, detection by microarray and ighcycler analysis). Comparison of the expression profiles of non-malignant cirrhotic liver tissues of HCV positive and negative patients showed a consistent overexpression of interferon-inducible genes specifically in HCV positive samples. These genes were strictly down-regulated in the malignant liver tissue of the same (HCV positive) patient.

Conclusions: Microarray data from liver tumor samples enables a fast and reliable differentiation between malignant and non-malignant liver tissue. Differentially expressed genes in HCV-induced HCC as well as cirrhotic liver tissues in comparison to non-viral induced HCC and liver cirrhosis were detectable. The most overexpressed gene in HCV positive HCC was the gene coding for SPINK1. Further studies using these data are ongoing to evaluate the potential role of these genes in viral hepatocarcinogenesis.