Study Of The Correlation Between Core Fucosylation Levels And Gastric Carcinoma

Background and Objective: Glycoprotein is widely distributed in the organism. It wasdivided into N-glycoprotein and O-glycoprotein according to different carbohydratechain structures. A lot of studies show that the N-glycoproteins are involved in manyimportant pathological processes such as inflammation, autoimmune diseases andmalignancies. Core-fucosylation is an important posttranslational modification ofproteins and the most important abnormal glycosylation in malignant tumors. More andmore studies show that core-fucosylation levels and activity of Fut8(which is the onlyglycosyltransferase involved in core-fucosylation) are closely related to many malignanttumors, but related research in gastric caner is still blank. The purpose of this study is toidentify the changes of gastric cancer related N-glycan profiling and explore the impactof core-fucosylation on biological behaviors of human gastric cancer cells.Methods: A total of244subjects including gastric cancer, gastric ulcer and healthycontrol were recruited. Serum N-glycan profiling was analyzed by DNAsequencer-assisted fluorophore-assisted capillary electrophoresis. The abundance of totalcore-fucosylation were analyzed by western blot, lectin blot and quantitative reversetranscription-polymerase chain reaction. The recombinant plasmids of α-1,6-fucosyltransferase and GDP-fucose transporter were constructed and thentransfected into gastric cancer cell lines BGC-823and SGC-7901. We used CCK-8andwound healing assay to assess the impact of core-fucosylation level on proliferation andmigration of gastric cancer cells.Results: We found characteristic serum N-glycan profiles in gastric cancer. Comparedwith the healthy control, non core-fucosylated peaks such as peak5(NA2) and peak9(NA3Fb) were increased significantly in gastric cancer (P<0.001). While thecore-fucosylated peaks such as peak2(NGA2FB), peak3(NG1A2F), peak6（NA2F）, peak7（NA2F）were significantly lower in gastric cancer(P<0.001).The total abundance of core-fucosylated residues(sumfuc) including peaks1,2,3,4,6and7wasalso significantly decreased(P<0.001). Consistently, lens culinaris agglutinin(LCA)-binding proteins were decreased significantly in serum of patients with gastriccancer (P<0.001), and α-1,6-fucosyltransferase was decreased significantly in gastrictumor tissues compared with that in paired adjacent non-tumor tissues (P<0.05).Upregulation of GDP-Tr and Fut8could inhibit the proliferation of gastric cancer cells,but it had no significant influence on migration.Conclusion: Core-fucosylation is down regulated in gastric cancer. Upregulation ofcore-fucosylation level could inhibit proliferation of the human gastric cancer cells, but ithad no significant influence on migration.