Gastric cancer (GC) is the second most common cause of cancer-related death, with nearly around 1 million cases per year. The progression of gastric cancer differs through a series of histologic stages that begins with gastritis and evolves over decades to atrophy (loss of glands), intestinal metaplasia, dysplasia, and finally adenocarcinoma. Thus, finding disease markers has become more crucial in identifying disease pathways. Due to the complexity of the proteome, glycosylation, a common post-translational modification of protein, has received increasing interest in the cancer community. In this study we aimed to evaluate the utility of native N-glycans in serum as biomarkers for the identification of GC progression pathways with respect to different diagnosis categories.
For the case-cohort study, we collected a subset of 72 serum samples from Mexico City. The sample set included four diagnostic categories: non-atrophic gastritis (NAG) (n = 18), duodenal ulcer (DU) (n = 18), intestinal-type gastric cancer (n = 18), and diffuse-type gastric cancer (DGC) (n = 18). 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-groups.
Candidate glycan markers isolated from serum were monitored in different disease stages including non-atrophic gastritis, duodenal ulcer, diffuse cancer and intestinal cancer. Around twenty N-glycan markers were significantly different in at least one way. Generally, fucosylated complex/hybrid type and high mannose type N-glycans showed stronger significance to differentiate gastric cancer, while NeuAc containing complex/hybrid type N-glycans were more significant in duodenal ulcer. Those glycans are usually correlated to IgG based serum protein. Our result will lead further studies to identify disease pathways from a glycomics point of view. Specificity and sensitivity of predicted values show promising results to distinguish gastric cancer from non-atrophic gastritis. In this study, we characterized potential glycan markers to differentiate gastric cancer and to identify disease progression pathways.