[Frontiers in Bioscience E3, 212-220, January 1, 2011]

Identifying serum biomarkers for TACE therapy efficiency of hepatocellular carcinoma

Chang-yu Li, Xiao-lin Wang, Jian-hua Wang, Zhi-ping Yan,Gao-quan Gong, Jie-min Cheng, Yi Chen, Ling-xiao Liu, Guo-ping Li, Cheng-gang Wang, Dong-hua Shi

Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Patients and blood sample preparation
3.2. Serum protein fractionation
3.3. Mass spectrometry analysis for profiling Serum proteome
3.4. Identification of differential peptides
3.5. Statistical methods, evaluation of marker efficacy
4. Results
4.1. Standards and standard serum spectrum
4.2. Unsupervised analysis of peptide ion signals from MS-based serum profiling differentiates before and after TACE
4.3. Marker efficiency confirmed with twice treated sera
4.4. Identification of peaks of proteins by mass spectrometry / mass spectrometry
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

Transcatheter Arterial Chemoembolization (TACE) is the first line of treatment in inoperable hepatocellular carcinoma. Magnetic affinity beads can be used to extract peptides from un-fractionated serum samples. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can detect the presence and the molecular mass of peptides. In this study, we used a highly optimized ClinProt-matrix-assisted laser desorption/ionization time-of flight mass spectrometer (MALDI-TOF-MS) to screen hepatocellular carcinoma markers for TACE. 40 sera from 20 patients, including before and after TACE to explore those biomarkers, might be related with therapy efficiency, and some of the patients who received another therapy were analyzed as well. The spectra were analyzed statistically using FlexAnalysis™ and Clin-Prot™ bioinformatic software. The seven most significant differential peaks (p<0.0.5) were selected out by ClinProTool software to identify hepatocellular carcinoma markers for TACE therapy. Furthermore, the differential peptide of 3883Da was identified as plasma serine protease inhibitor precursor (Protein C inhibitor). This study provides a direct link between peptide marker profiles and TACE therapy, and the markers may have clinical utility for monitoring efficiency of therapy.