人脑胶质瘤组织中Spinophilin的表达及临床意义

Expression of Spinophilin in human glioma tissues and its clinical significance

目的探讨Spinophilin在人脑胶质瘤和非瘤脑组织中的表达差异,分析其表达与胶质瘤病理分级、IDH分型及患者预后的关系。方法应用公共数据库分析Spinophilin在不同级别、不同亚型脑胶质瘤中的表达及与患者预后的关系。采用qRT-PCR、免疫组化和Western blot法检测其在非瘤脑组织和胶质瘤组织中的表达。结果分析TCGA胶质瘤数据库和应用qRT-PCR检测2016年2月~2018年2月徐州医科大学附属医院收治的胶质瘤标本发现,Spinophilin mRNA水平在WHOⅣ级胶质瘤中明显低于非瘤脑组织(P<0.05);分析GSE16011和GSE4290胶质瘤数据集发现,Spinophilin mRNA水平在WHOⅢ级(P<0.01)和Ⅳ级(P<0.001)胶质瘤中均显著下调。IDH1野生型胶质瘤较IDH1突变型胶质瘤中Spinophilin mRNA表达下调,其中在GSE16011(P<0.05)和CGGA(P<0.001)胶质瘤数据集中差异具有统计学意义。免疫组化检测发现,与非瘤脑组织相比,WHOⅡ级和Ⅲ级胶质瘤中Spinophilin蛋白明显降低(P<0.01);Western blot分析发现,Spinophilin在不同级别胶质瘤中均表达下调,在WHOⅣ级胶质瘤中下调差异具有统计学意义(P<0.01)。CGGA胶质瘤数据库生存分析显示,Spinophilin高表达胶质瘤患者的总生存时间显著长于低表达患者(P<0.0001);进一步分析发现,Spinophilin在WHOⅡ级(P=0.041)和Ⅲ级(P=0.033)胶质瘤中高表达与患者较长的生存期相关。结论Spinophilin高表达胶质瘤患者的预后较好,有望成为脑胶质瘤分子病理诊断和预后评估的生物标志物。

Purpose To explore the differences in the expression of Spinophilin in human glioma tissues and non-tumor brain tissues,and to analyze the relationship between its expression levels and pathological grade,IDH subtype,and patients′prognosis.Methods Public databases were used to analyze the expression changes of Spinophilin in different grades and different subtypes of glioma tissues,and its relationship with patients′prognosis.Quantitative real-time PCR(qRT-PCR),immunohistochemistry(IHC)and Western blot were used to detect the expression levels of Spinophilin in non-tumor brain tissues and glioma tissues.Results Analysis of TCGA glioma database and qRT-PCR measurements in our collected glioma samples showed that Spinophilin mRNA level in WHOⅣglioma tissues was significantly lower than that of nontumor brain tissues(P<0.05).Analysis of GSE16011 and GSE4290 glioma datasets showed that the level of Spinophilin mRNA was significantly decreased in WHOⅢ(P<0.01)and WHOⅣ(P<0.001)glioma tissues.In addition,the expression of Spinophilin mRNA in IDH1 wild-type gliomas was lower than that of IDH1 mutant,and it reached statistical differences in the glioma datasets of GSE16011(P<0.05)and CGGA(P<0.001).Compared with nontumor brain tissue,immunohistochemical analysis showed that Spinophilin protein level was significantly reduced in WHOⅡand WHOⅢglioma tissues(P<0.01),and Western blot analysis showed that it was downregulated in different grades of glioma tissues,and the difference was statistically significant in WHOⅣgliomas(P<0.01).Survival analysis of CGGA glioma database showed that the overall survival time of patients with high expression of Spinophilin in WHOⅡ-Ⅳglioma was significantly longer than those with low expression of Spinophilin(P<0.0001).Further analysis showed that higher expression of Spinophilin in WHOⅡ(P=0.041)and WHOⅢ(P=0.033)gliomas was associated with longer survival time in patients.Conclusion High expression of Spinophilin predicts good prognosis in glioma patients,and it may be a promising biomarker for molecular pathological diagnosis and prognostic evaluation in gliomas.