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


CONCLUSIONS
The NAP-2 may be a specific proteomic biomarker of hepatitis B-related HCC.
He
Min
M
Medical Scientific Research Center, Guangxi Medical University, Nanning, P. R. China. hemimmim@yahoo.com
Qin
Jian
J
Zhai
Rihong
R
Wei
Xiao
X
Wang
Qi
Q
Rong
Minhua
M
Jiang
Zhihua
Z
Huang
Yuanjiao
Y
Zhang
Zhiyong
Z