Detection and identification of NAP-2 as a biomarker in hepatitis B-related hepatocellular carcinoma by proteomic approach

Min He¹ , Jian Qin² , Rihong Zhai³ , Xiao Wei² , Qi Wang¹ , Minhua Rong² , Zhihua Jiang² , Yuanjiao Huang¹ and Zhiyong Zhang²

¹Medical Scientific Research Center, Guangxi Medical University, Nanning, 530021, P. R. China

²School of Public Health, Guangxi Medical University, Nanning, 530021, P. R. China

³Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA

author email corresponding author email

Proteome Science 2008, 6:10doi:10.1186/1477-5956-6-10


Published:	10 March 2008

Abstract

Background

A lack of sensitive and specific biomarkers is a major reason for the high rate of Primary hepatocellular carcinoma (HCC)-related mortality. The aim of this study was to investigate potential proteomic biomarkers specific for HCC.

Methods

81 patients with hepatitis B-related HCC and 33 healthy controls were randomly divided into a training set (33 HCC, 33 controls) and a testing set (48 HCC, 33 controls). Serum proteomic profiles were measured using Surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS).) A classification tree was established by Biomarker Pattern Software (BPS). Candidate SELDI peaks were isolated by tricine-SDS-PAGE, identified by HPLC-MS/MS and validated by immunohistochemistry (IHC) in liver tissues.

Results

A total of 6 proteomic peaks (3157.33 m/z, 4177.02 m/z, 4284.79 m/z, 4300.80 m/z, 7789.87 m/z, and 7984.14 m/z) were chosen by BPS to establish a classification tree with the highest discriminatory power in the training set. The sensitivity and specificity of this classification tree were 95.92%, and 100% respectively in the testing set. A candidate marker of about 7984 m/z was isolated and identified as neutrophil-activating peptide 2 (NAP-2). IHC staining showed that NAP-2 signals were positive in HCC tissues but negative in adjacent tissues.

Conclusion

The NAP-2 may be a specific proteomic biomarker of hepatitis B-related HCC.