SELDI-TOF-MS Profiling of serum for detection of liver cirrhosis and hepatocellular carcinoma in chronic hepatitis C

Abstract

The aim of the present study was to establish protein profiles using surface enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) for identification of liver cirrhosis and hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. Serum samples of 40 patients with F1/F2 fibrosis, 44 patients with F4 fibrosis, 34 patients with HCC were applied to CM 10 cation exchange protein chips and analysed using the SELDI-TOF ProteinChip System (PBS-IIc; Ciphergen Biosystems) after anion-exchange fractionation. Fibrosis stage and HCC had been histologically confirmed in all patients. Data were analysed for protein patterns by multivariate statistical techniques and artificial neural networks. A 4 peptide/protein multimarker panel correctly identified HCCs with a sensitivity of 100% and specificity of 84% in the HCV-cirrhosis versus HCV-HCC training sample set. Sensitivity and specificity for HCC were 68% and 80% for an internal cross validated test sample set. Cirrhotic patients could be discriminated against patients with F1 or F2 fibrosis using a 5 peptide/protein multimarker pattern with a specificity of 100% and a sensitivity of 85%. Whereas the internal cross validation test set displayed sensitivity and specificity for liver cirrhosis of 80% and 67%, respectively. 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. Due to the suitability of the SELDI-TOF-MS/ProteinChip technology for mass application it might become a tool for screening HCV patients for cirrhosis and HCC.