TMED2在胃癌中的表达和对预后的影响及作用机制

    The expression of TMED2 in gastric cancer and its impact on prognosis and mechanism of action

    • 摘要:
      目的 探究TMED2在胃癌中的表达情况和对病人临床预后的影响及可能作用机制。
      方法 采用免疫组织化学技术检测TMED2在胃癌组织及癌旁组织中的表达水平,分析TMED2表达水平与临床病理参数及术后5年生存率的关系。生物信息学预测TMED2的功能,利用慢病毒调控胃癌MGC-803细胞TMED2的表达,并分析TMED2对胃癌细胞周期进程、增殖、迁移和侵袭的影响。
      结果 免疫组织化学检测结果显示TMED2在胃癌组织中高表达(P < 0.01),且其表达量与外周血肿瘤标志物CEA和CA19-9水平呈正相关(r=0.604, 0.581, P < 0.01)。单因素及多因素分析显示TMED2高表达(HR=3.155,95%CI:1.740~5.721)是影响胃癌术后5年生存率的独立危险因素。富集分析提示TMED2的功能和细胞周期有关。流式细胞术检测表明上调TMED2促进G1/S细胞周期的转化,下调则抑制(P < 0.05);Western blotting结果显示下调TMED2抑制胃癌细胞DK4和Cyclin D2蛋白的表达,上调则促进(P < 0.05)。CCK-8和Transwell检测显示上调TMED2促进胃癌细胞的增殖、迁移和侵袭,下调则相反(P < 0.05)。
      结论 TMED2在胃癌组织中高表达并影响病人临床预后,可能与调控胃癌细胞周期进程和恶性生物学行为有关。

       

      Abstract:
      Objective To explore the expression of transmembrane emp24 domain protein 2 (TMED2) in gastric cancer and its impact on clinical prognosis, and its possible mechanism.
      Methods Immunohistochemical techniques were used to detect the expression level of TMED2 in gastric cancer tissues and adjacent tissues, and the relationship between TMED2 expression and clinicopathological parameters and postoperative 5-year survival rate was analyzed.The function of TMED2 was predicted by bioinformatics.Lentivirus was used to regulate the expression of TMED2 in gastric cancer MGC-803 cell line, and the effect of TMED2 on the cycle progression, proliferation, migration and invasion of gastric cancer cells was further analyzed.
      Results Immunohistochemistry results showed that TMED2 was highly expressed in gastric cancer tissues (P < 0.01), and its expression was positively correlated with the level of tumor markers CEA and CA19-9 in peripheral blood(r=0.604, 0.581, P < 0.01).Univariate and multivariate analysis showed that high expression of TMED2 (HR=3.155, 95%CI: 1.740-5.721) was an independent risk factor affecting the 5-year survival rate after radical gastrectomy.Enrichment analysis indicated that the function of TMED2 was related to the cell cycle.Flow cytometry illustrated that up-regulation of TMED2 promoted G1/S cell cycle transition, while downregulation inhibited it (P < 0.05).Western blotting results displayed that down-regulation of TMED2 inhibited the expression of CDK4 and cyclin D2 proteins in gastric cancer cells, while up-regulation promoted it (P < 0.05).CCK-8 and Transwell assays showed that up-regulation of TMED2 promoted the proliferation, migration and invasion of gastric cancer cells, while down-regulation was the opposite (P < 0.05).
      Conclusions TMED2 is highly expressed in gastric cancer tissues and affects the clinical prognosis of patients, which may be related to the regulation of gastric cancer cell cycle progression and malignant biological behavior.

       

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