Identification and Confirmation of Increased Fibrinopeptide A Serum Protein Levels in Gastric Cancer Sera by Magnet Bead Assisted MALDI-TOF Mass Spectrometry

Abstract

Gastric cancer is the second most common malignancy and prognosis remains dismal. The reasons for the poor prognosis are the lack of sensitive serum markers for early detection and screening of high-risk individuals as well as the limited treatment options in advanced cancer stages. Using MALDI-TOF mass spectrometry after prefractionation of sera with magnet hydrophobic C8 coated beads sera from 14 patients with gastric cancer and 14 healthy controls mass spectra were generated. A peptide fragment was found to be highly elevated in cancer sera and was identified as fibrinopeptide A. To confirm proteome analysis of gastric cancer sera, we then screened a larger series of patients with gastric cancer (n = 99), high-risk individuals (n = 13) and normal controls (n = 111) for fibrinopeptide A serum levels. Interestingly, the mean logarithmic concentrations of serum fibrinopeptide A levels were significantly higher in cancer patients (mean 3.636 +/- 0.3738; p < 0.0001) and high-risk individuals (mean 3.569 +/- 0.4722; p < 0.05) compared to normal controls (mean 3.303 +/- 0.4012). In contrast, we observed no association of fibrinopeptide A levels with tumor stage, tumor location, presence of regional or distant metastasis, and Lauren type of gastric cancer. In conclusion, MALDI-TOF mass spectrometry of prefractionated gastric cancer sera allows the identification of potential biomarkers that may lead to the development of serum based tests for screening of high-risk individuals.

Meta-analysis of associations between MDM2 SNP309 polymorphism and gastric cancer risk

“…The overall prognosis for patients with GC remains poor and the 5-year survival rates range from 10 to 28% (4). The mechanisms that result in the tumorigenesis and progression of GC remain to be elucidated, but etiological factors include interactions between genetic and environmental factors.…”

Metabolic derangements identified through untargeted metabolomics in a cross-sectional study of Nigerian children with severe acute malnutrition

“…FPA is a 16 amino acid peptide produced upon cleavage of the fibrinogen alpha chain by thrombin during the coagulation cascade. Thus it is an indicator of thrombosis, and is elevated in plasma during a number of inflammatory conditions including Crohn's disease, gastric cancer, and coronary thrombosis (Eisenberg et al 1985;Edwards et al 1987;Ebert et al 2006). As the intact peptide was not elevated in SAM, these fragments are not simply a result of increased inflammation and thrombosis, but have another unknown origin.…”

Epstein-Barr virus DNA associated with gastric adenocarcinoma and adjacent non-cancerous mucosa in patients from Manaus, Brazil

“…Gastric cancer (GC) is one of the most common cancers, and is ranked 2nd among the worldwide cancer mortality rates (Ebert et al, 2006). Several factors may contribute individually or together to the emergence of this neoplasia, including infection with Helicobacter pylori, dietary habits, genetic factors, and viral infections (Schulz, 2005).…”

“…GC is mostly found in individuals aged over 50 years; its incidence in individuals under 40 years corresponds to only 5% of all cases (Theuer et al, 1996;Mauad et al, 2000). Most patients are diagnosed with GC in an advanced state, thus drastically reducing the treatment options, survival, and cure (Ebert et al, 2006). In the northern part of Brazil, GC is the 2nd most common cancer in men and the 4th in women, accounting for an estimated 13 and 7 new cases per 100,000 per year for men and women, respectively (Guerra et al, 2005;INCA, 2012).…”