Session Title: Category 5g. VIRAL HEPATITIS: g. HEPATITIS C - CLINICAL (THERAPY)
Presentation Date: Apr 15, 2010
SELDI PROTEINCHIP SERUM ANALYSIS TO PREDICT VIROLOGICAL RESPONSE IN PATIENTS WITH CHRONIC HEPATITIS C TREATED WITH PEGYLATED INTERFERON PLUS RIBAVIRIN
N. Fujita1*, K. Mihara2, J. Mukai2, Y. Yanohara2, R. Sugimoto1, Y. Kobayashi1, Y. Naito3, T. Ichida4, M. Kaito5, T. Yoshikawa3, Y. Takei1
1Department of Gastroenterology and Hepatology, Institute of Medical Sciences, Mie University Graduate School of Medicine, Mie, 2Biomarker Science Co. Ltd., Osaka, 3Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, 4Department of Gastroenterology, Juntendo University School of Medicine, Shizuoka Hospital, Shizuoka, 5Mie Gastroenterological Clinic, Mie, Japan. *email@example.com
Background and aims: Recent development of proteomic array technology, including protein profiling coupling ProteinChip array with surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF/MS), provides a potentially powerful tool for discovery of new biomarkers by comparison of its profiles according to patient phenotypes. We used this approach to identify the new biomarkers to predict treatment response in patients with chronic hepatitis C receiving a 48 week course of pegylated interferon α-2b (PEG-IFN) plus ribavirin (RBV) therapy.
Methods: Protein profiles of 32 patients' pretreatment serum samples (Male/Female = 16/16, mean age = 56.9 ± 7.3 yr, and all were infected with genotype 1b and high viral loads) (SVR/non-SVR = 10/22) were conducted by SELDI-TOF/MS method using the different three ProteinChip arrays (CM10, Q10, IMAC30). Several proteins which showed statistically significantly different peak intensities between SVR and non-SVR were extracted, purified, and identified by chromatograpy, SDS-PAGE, TOF/MS, and MS/MS assay.
Results: Using SELDI-TOF/MS, 11 peak intensities were significantly different between SVR and non-SVR patients, 3 of them were decreased and 8 increased in non-SVR. The eight non-SVR increased protein peaks were identified as 4 apolipoprotein fragments, 2 iron-related (transferrin and hemopexin), and 2 fibrogenesis-related (CTAP-III, platelet factor-4) proteins fragments, respectively. Multivariate analysis showed that the serum ferritin and 3 peak intensity values (ApoA1, hemopexin, and transferrin) were independent variables associated with non-SVR, and the area under the Receiver Operator Characteristic (ROC) curves for non-SVR prediction by using the ApoA1/hemopexin and hemopexin/transferrin were 0.964 and 0.936.
Conclusions: SELDI-TOF/MS protein profile comparison between SVR and non-SVR is useful for prediction of treatment outcome in patients with chronic hepatitis C receiving PEG-IFN plus RBV. Further, this technique may also provide an inference into the mechanisms of treatment resistance.