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.