Serum Glycan Signatures of Gastric Cancer

Abstract

Glycomics, a comprehensive study of glycans expressed in biological systems, is emerging as a simple yet highly sensitive diagnostic tool for disease onset and progression. This study aimed to use glycomics to investigate glycan markers that would differentiate patients with gastric cancer (GC) from those with non-atrophic gastritis (NAG). Patients with duodenal ulcer (DU) were also included because they are thought to represent a biologically different response to infection with Helicobacter pylori, a bacterial infection that can cause either GC or DU. We collected 72 serum samples from patients in Mexico City that presented with NAG, DU, or GC. N-glycans were released from serum samples using the generic method with PNGase F and were analyzed by MALDI FT-ICR MS. The corresponding glycan compositions were calculated based on accurate mass. ANOVA based statistical analysis was performed to identify potential markers for each sub-group. Nineteen glycans were significantly different among the diagnostic groups. Generally, decreased levels of high-mannose type glycans, glycans with one complex type antenna, bigalactosylated biantennary glycans, and increased levels of non-galactosylated biantennary glycans were observed in gastric cancer cases. Altered levels of serum glycans were also observed in DU, but differences were generally in the same direction as GC. Serum glycan profiles may provide biomarkers to differentiate GC cases from controls with NAG. Further studies will be needed to validate these findings as biomarkers and identify the role of protein glycosylation in GC pathology.

The serum immunoglobulin G glycosylation signature of gastric cancer

“…In this pilot study it was observed that levels of several truncated glycans, where the galactose is missing on at least one arm, are increased with gastric cancer, while levels of several fully galactosylated bi- and tri- antennary structures were decreased (Table 2). We recently reported the association of increased levels of non-galactosylated biantennary glycans with gastric cancer in total serum in the same cohort [21]. The results reported here differ in that we have now identified glycan profiles specifically on IgG that are associated with gastric cancer.…”

“…[13-15]), but also various types of cancer (e.g. [16-20]), including gastric cancer [21]. This indicates that protein glycosylation may reflect one’s balanced physiological state, and is affected by most disease states.…”

“…The majority of glycomic studies performed to date have focused on the global glycomic analysis of plasma or serum [20], including our resent studies on gastric cancer [21]. These approaches rely on the comprehensive release of glycans from proteins, but ignore any protein correlation.…”

Biomarkers for Helicobacter Pylori Infection and Gastroduodenal Diseases

“…Ozcan et al examined native glycans via MS in the sera of patients with gastric cancer and nonatrophic gastritis in Mexico [63]. As a result, 19 glycans were associated with gastric cancer.…”

Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration

“…The factors that determine whether peptic ulceration or gastric cancer develops in individual humans are not completely understood, but several factors are relevant, including features of the H. pylori strain with which the host is infected, host genetic characteristics, and in the case of gastric cancer, host diet (26)(27)(28)(29)(30)(31)(32). Specifically, increased dietary salt intake and decreased dietary iron intake are associated with an increased risk of gastric cancer in H. pylori-infected humans and in experimentally infected gerbils (33)(34)(35)(36)(37)(38)(39)(40)(41)(42).…”