Expression of β-1,6 glucosaminyl (N-acetyl) transferase 2 in gastric cancer and its clinical significance
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Abstract:
Objective: To investigate the expression level of glucosaminyl (N-acetyl) transferase 2 (GCNT2) in gastric cancer (GC) tissues and its role in the occurrence, development, diagnosis and prognosis of GC. Methods: By using TIMER, GEPIA2, Oncomine and UALCAN databases as well as clinical specimens of GC tissues and paired para-cancerous tissues from 25 GC patients who had surgical resection in the Affiliated Hospital of Binzhou Medical University from January 2018 to December 2019, the expression level of GCNT2 gene in GC tissues and its diagnostic and prognostic value in GC were analyzed. The main signal pathways that GCNT2 involved in and the correlation of GCNT2 with immune infiltration were analyzed by LinkedOmics, GSEA and ssGSEA. pc-GCNT2 and its negative control plasmids were transfected into gastric cancer SGC-7901 and BGC-823 cells. Colony formation assay and Traswell assay were used to detect the effect of GCNT2 on the proliferation and invasion of GC cells. WB method was used to detect the protein expression of GCNT2, STAT3 and PD-L1 in transfected cells. Results: The expression level of GCNT2 mRNA in GC tissues was significantly lower than that in para-cancerous tissues (P<0.05), and its expression level was significantly correlated with the prognosis of patients (P<0.05), which is of high value in the diagnosis of GC. The methylation status of GCNT2 in GC tissues was significantly higher than that in para-cancerous tissues. The biological processes that GCNT2 gene involved in were mainly cell morphogenesis, intercellular adhesion, multicellular biological signals and synaptic transmission, etc. Single gene GSEA analysis showed that GCNT2 mainly inhibited IL-6/JAK/STAT3 and IL-2/STAT5 signaling pathways, inflammatory response, α/γ interferon response and NF-κB expression in GC. There was a significant correlation between the expression of GCNT2 and immune infiltration in GC tissues. Over-expression of GCNT2 significantly inhibited the proliferation and invasion of GC cells (all P<0.01), and down- regulated the expression of STAT3 and PD-L1 (all P<0.01). Conclusion: GCNT2 is significantly lowly expressed in gastric cancer tissues, and is significantly related to the diagnosis and prognosis of GC patients. GCNT2 plays an important role in the occurrence and development of GC mainly through inhibiting IL-6/JAK/STAT3 signaling pathway and immune-related carcinogenic signaling pathway.