目的： 探讨β-1,6 N-乙酰氨基葡萄糖转移酶2 （GCNT2）基因在胃癌（GC）组织中的表达及其在GC发生、发展和诊断及预后中的作用。 方法： 利用TIMER、GEPIA2、Oncomine和UALCAN等数据库数据，以及2018年1月至2019年12月滨州医学院附属医院手术切除的25例GC患者的癌和配对癌旁组织标本，分析GCNT2基因在GC组织中的表达及其在GC诊断和预后中的价值，利用LinkedOmics、GSEA和ssGSEA分析GCNT2所涉及的主要信号通路及其与免疫浸润之间的相关性。将pc-GCNT2及其阴性对照质粒转染进胃癌SGC-7901和BGC-823细胞，用克隆形成实验和Transwell实验检测GCNT2对GC细胞增殖和侵袭的影响，WB法检测细胞中GCNT2、STAT3和PD-L1蛋白的表达水平。 结果： GCNT2 mRNA在GC组织中的表达水平显著低于癌旁组织（P<0.05或P<0.01），其表达水平与患者预后显著相关（P<0.05），其对GC诊断有较高的价值。GCNT2在GC组织中的甲基化状态显著高于癌旁组织，GCNT2基因参与的生物过程主要是参与细胞形态发生的成分、细胞间黏附、多细胞生物信号和突触传递等。单基因GSEA分析发现，GCNT2在GC中主要抑制IL-6/JAK/STAT3、IL-2/STAT5信号通路和炎症反应、α/γ干扰素响应与NF-κB表达等。GCNT2的表达与GC组织的免疫浸润具有显著相关性。过表达GCNT2可显著抑制GC细胞的增殖和侵袭能力（均P<0.01），降低细胞中STAT3和PD-L1的表达水平（均P<0.01）。 结论： GCNT2基因在GC组织中低表达，与GC的诊断及预后显著相关，其主要通过抑制IL-6/JAK/STAT3和免疫相关致癌信号通路而在GC的发生、发展中发挥重要的作用。

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.

R735.2；R730.2；R730.7

山东省自然科学基金资助项目（No.ZR2017LH050）