Identification of carboxyl terminal peptide of Fibrinogen as a potential serum biomarker for gastric cancer

Abstract

Gastric cancer (GC) is a very common disease worldwide where new serum biomarkers are urgently needed to improve their early diagnosis. In this study, we aim to search for the potential serum protein/peptide biomarkers of GC by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). We first obtained the serum protein/peptide profiles from a training dataset including 30 patients with GC, 16 cases with chronic benign gastric disease (CGD), and 30 normal controls (CON) where 15 protein peaks were identified to exhibit the obvious deviation (P < 0.001, Wilcoxon rank sum test) among GC, CGD, and CON analyzed by Biomarker Wizard 3.1 software with three protein peaks with mass-to-charge (m/z) ratio 5910, 5342, and 6439 further confirmed in the validation dataset. Among the three protein peaks, peak 5910 displayed the most significantly different which could distinguish GC patients from CGD and CON with a sensitivity of 86.3 %, a specificity of 91.3 %, and the area under the receiver operating characteristic curve (AUC) of 0.89 by using the optimal cutoff value of 17.3. We further identified peak 5910 as the carboxyl terminal fraction of Fibrinogen α by LC-MS and validated its identity by antiserum-mediated SELDI-based immunodepletion assays. In sum, SELDI-TOF-MS method could effectively generate serum peptidome in cancer patients and provide a new approach to identify potentially diagnostic and prognostic biomarkers for cancer. The carboxyl terminal fraction of Fibrinogen α may be a potential serological biomarker for GC diagnosis.

Keywords: Biomarker; Diagnosis; Gastric cancer; Proteomics; SELDI.