腺苷A3受体促进胶质瘤上皮间质转化及其对预后的影响OA

Objective To investigate the expression of adenosine A3 receptor(ADORA3)in human glioma and its effects on prognosis and epithelial-mesenchymal transition.Methods The mRNA expression data and corresponding clinical information of ADORA3 were obtained from TCGA,CGGA,Rembrandt,Gravendeel and Gill databases,and the effects of ADORA3 expression on the prognosis of glioma patients and the process of epithelial-mesenchymal transition were analyzed.The surgically resected glioma samples of 35 cases,along with non-tumor brain tissues of 7 cases obtained from decompression surgery for severe craniocerebral injury were collected in the Department of Neurosurgery at Renmin Hospital of Wuhan University from July 2023 to April 2024,and the ADORA3 expression was detected by immunohistochemical staining.Glioblastoma multiforme(GBM)cells of U87 and U251 were transfected with NcRNA and SiRNA,respectively,as the control group and the knockdown group,and the effects of ADORA3 on cell invasion ability and epithelial-mesenchymal transition related proteins were analyzed by Transwell and Western blot.Results Bioinformatics analysis and immunohistochemical staining showed that the expression level of ADORA3 in human glioma tissues was significantly higher than that in non-tumor brain tissues(P<0.05),and the expression of ADORA3 was associated with glioma WHO grading(P<0.05).Kaplan-Meier survival curve analysis in TCGA,CGGA,Rembrandt and Gravendeel databases showed that the overall survival rate of patients with high ADORA3 expression was significantly lower than that of patients with low ADORA3 expression(P<0.001);and Cox regression analysis showed that high expression of ADORA3 was an independent risk factor for poor prognosis in patients with glioma(P<0.05);the expression level of ADORA3 in the mesenchymal type of GBM patients was significantly higher than that of the classical type and the proneural type;furthermore,ADORA3 showed significant correlations with epithelial-mesenchymal transition related markers of Vimentin,SNAI1,SNAI2,TWIST1,TWIST2,MMP2,CD44,and FN1.The knockdown of ADORA3 in vitro reduced the cell invasive ability,decreased the expression levels of MMP2,Vimentin,and SNAI1 proteins,and increased the expression of E-cadherin,with statistically significant differences(P<0.05).Conclusion ADORA3 is highly expressed in glioma,which can promote the process of epithelial-mesenchymal transition in patients,and serve as an independent risk factor for poor prognosis.