Brief Article
Copyright ©2014 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 21, 2014; 20(11): 3025-3032
Published online Mar 21, 2014. doi: 10.3748/wjg.v20.i11.3025
Mass spectrometry-based serum peptide profiling in hepatocellular carcinoma with bone metastasis
Jian He, Zhao-Chong Zeng, Zuo-Lin Xiang, Ping Yang
Jian He, Zhao-Chong Zeng, Zuo-Lin Xiang, Ping Yang, Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Author contributions: He J and Zeng ZC designed the research; He J and Xiang ZL performed the research; Yang P contributed new reagents and analytic tools; He J and Zeng ZC analyzed the data; He J, Zeng ZC, Xiang ZL and Yang P wrote the paper.
Supported by the Medical Guidance Program of the Science and Technology Commission of Shanghai Municipality, No. 10411962400
Correspondence to: Zhao-Chong Zeng, Professor, Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. zeng.zhaochong@zs-hospital.sh.cn
Telephone: +86-21-64041990 Fax: +86-21-64041990
Received: August 21, 2013
Revised: December 5, 2013
Accepted: January 2, 2014
Published online: March 21, 2014
Abstract

AIM: To investigate the potential of serum peptides as a diagnostic tool for hepatocellular carcinoma (HCC) with bone metastasis.

METHODS: Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) was used to characterize the serum peptide profile of HCC patients with bone metastasis. Serum samples from 138 HCC patients (66 cases with and 72 cases without bone metastasis) were randomly assigned into a training set (n = 76) and a test set (n = 62). Differential serum peptides were examined using ClinProt magnetic bead-based purification followed by MALDI-TOF-MS. The sequences of differentially expressed serum peptides were identified using liquid chromatography-mass spectrometry. A diagnostic model was established using a learning algorithm of radial basis function neural network verified by a single blind trial. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic power of the established model.

RESULTS: Ten peptide peaks were significantly different between HCC patients with or without bone metastasis (P < 0.001). Sequences of seven peptides with mass to charge ratios (m/z) of 1780.7, 1866.5, 2131.6, 2880.4, 1532.4, 2489.8, and 2234.3 were successfully identified. These seven peptides were derived from alpha-fetoprotein, prothrombin, serglycin, isoform 2 of inter-alpha-trypsin inhibitor heavy chain H4, isoform 1 of autophagy-related protein 16-2, and transthyretin and fibrinogen beta chains, respectively. The recognition rate and predictive power of a diagnostic model established on the basis of six significant peptides (m/z for these six peptides were 1535.4, 1780.7, 1866.5, 2131.6, 2880.4, and 2901.9) were 89.47% and 82.89%, respectively. The sensitivity and specificity of this model based upon a single blind trial were 85.29% and 85.71%, respectively. ROC analysis found that the AUC (area under the ROC curve) value was 0.911.

CONCLUSION: Our study suggested that serum peptides may serve as a diagnosis tool for HCC bone metastasis.

Keywords: Hepatocellular carcinoma, Serum, Peptides, Matrix-assisted laser desorption ionization-time of flight mass spectrometry, Tumor biomarker

Core tip: Advances in the diagnosis and treatment of hepatocellular carcinoma (HCC) and extension of overall survival rates have led to an increase in the incidence of bone metastasis of HCC, which accounts for approximately 38.5% of all cases of extrahepatic metastasis of HCC. The patient’s quality of life would significantly be affected by the time of diagnosis. However, early diagnostic molecular markers for bone metastasis from HCC have not yet been identified. In this study, we performed differential serum peptide profiling in HCC patients with bone metastasis, which can be used for early prediction of this disorder.