[Frontiers in Bioscience E2, 961-971, June 1, 2010]

Identification of novel serum biomarkers for gastric cancer by magnetic bead

Wentao Liu1, Xiang Gao1, Qu Cai1, Jianfang Li1, Zhenglun Zhu1, Chen Li1, Xuexin Yao1, Qiumeng Yang1, Ming Xiang1, Min Yan1, Zhenggang Zhu1

1Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai Institute of Digestive Surgery, Shanghai 200025, PR 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 to profile serum proteome
3.4. Statistical methods, evaluation of diagnostic efficacy
3.5. Identification of protein markers
4. Results
4.1. Identification of serum proteomic features associated with gastric cancer
4.2. Sensitivities and specificities of the biomarkers by receiver operating characteristic (ROC) curve analysis
4.3.Establishment and validation of gastric cancer predicting model
4.4. Identification of the cancer markers
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

Early diagnosis and early treatment is known to improve prognosis for gastric cancer. 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. MALDI-TOF-MS mass spectra of peptides and proteins were generated after WCX CLINPROT bead fractionation of 62 gastric cancer serum samples. The discovery set consisted of 44 samples while the validation set was 18 serum samples. The spectra were analyzed statistically using flexAnalysisTM and Clin-ProtTM bioinformatic software. The six most significant peaks were selected out by ClinProTool software and utilized to train a Supervised Neural Network to identify gastric cancer sera from control sera. The sensitivity and specificity of the model when tested on the validation set were 100% and 75%, respectively. A set of 6 peptides that can be used to distinguish serum from gastric cancer patients with good sensitivity and specificity were identified, and these peptides may be useful biomarkers to distinguish cancer individuals who may benefit from radiologic or endoscopic examination.