脑胶质瘤组织中GLP-1R和DPP4表达及临床预后价值

The expression and clinical prognostic value of GLP-1R and DPP4 in glioma tissue

目的研究脑胶质瘤组织中胰高血糖素样肽-1受体(GLP-1R)、二肽基肽酶4(DPP4)的表达和临床意义。方法选取2016年1月—2018年1月武汉市第一医院神经外科手术治疗的脑胶质瘤患者88例的胶质瘤组织及癌旁组织,石蜡包埋切片。应用免疫组织化学检测组织中GLP-1R、DPP4蛋白的表达。Spearman秩相关分析脑胶质瘤组织中GLP-1R与DPP4表达的相关性。统计分析GLP-1R、DPP4蛋白表达与脑胶质瘤患者临床病理特征的关系。KaplanMeier生存分析(Log-rank检验)GLP-1R、DPP4表达与患者生存预后的关系。多因素Cox回归分析影响脑胶质瘤患者预后的危险因素。结果脑胶质瘤组织中GLP-1R、DPP4蛋白表达阳性率高于癌旁组织(χ^(2)/P=34.680/<0.001,24.908/<0.001)。脑胶质瘤组织中GLP-1R与DPP4蛋白表达呈显著正相关(r/P=0.604/<0.001)。Kamofsky功能状态(KPS)评分<70分及WHO分级Ⅲ级脑胶质瘤患者GLP-1R、DPP4蛋白表达阳性率高于KPS评分≥70分、WHO分级Ⅰ~Ⅱ级患者(GLP-1R:χ^(2)/P=8.005/0.005、7.883/0.005;DPP4:χ^(2)/P=7.062/0.008、6.471/0.011)。GLP-1R、DPP4阳性表达脑胶质瘤患者5年总体生存率分别低于GLP-1R、DPP4阴性表达者(χ^(2)/P=10.128/<0.001,9.670/0.003)。多因素Cox回归分析结果显示,脑胶质瘤组织中GLP-1R阳性表达、DPP4阳性表达、WHO分级Ⅲ级及KPS评分<70分是影响患者生存预后的独立危险因素[HR(95%CI)=2.427(1.426~4.569),1.740(1.121~2.568),2.671(1.160~6.012),1.628(1.017~2.592)]。结论脑胶质瘤组织中GLP-1R、DPP4表达升高,是影响脑胶质瘤患者生存预后的独立危险因素。

Objective To study the expression and clinical significance of Glucagon-like peptide-1 receptor(GLP-1R)and dipeptidyl peptidase 4(DPP4)in glioma.Methods From January 2016 to January 2018,88 cases of glioma tissues and paracancerous tissues of brain glioma patients who were treated by Neurosurgery of Wuhan First Hospital were selected,and paraffin embedded sections were made.Apply immunohistochemistry to detect the expression of GLP-1R and DPP4 proteins in tissues.Spearman rank correlation analysis of the correlation between GLP-1R and DPP4 expression in glioma tissue.Statistical analysis of the relationship between the expression of GLP1R and DPP4 proteins and the clinical and pathological characteristics of glioma patients.Kaplan Meier survival analysis(Log rank test):The relationship between GLP-1R,DPP4 expression and patient survival prognosis.Multivariate Cox regression analysis of risk factors affecting the prognosis of glioma patients.Results The positive rates of GLP-1R and DPP4 protein expression in glioma tissues are significantly higher than those in adjacent tissues(χ^(2)/P=34.680/<0.001,24.908/<0.001).There is a significant positive correlation between GLP-1R and DPP4 protein expression in glioma tissue(r/P=0.604/<0.001).The positive rates of GLP-1R and DPP4 protein expression in patients with Kamofesky functional status(KPS)score<70 and WHO grade III glioma were higher than those in patients with KPS score≥70 and WHO grade I-II glioma(GLP-1R:χ^(2)/P=8.005/0.005,7.883/0.005;DPP4:χ^(2)/P=7.062/0.008,6.471/0.011).The overall 5-year survival rate of glioma patients with GLP-1R and DPP4 positive expression is lower than that of GLP-1R and DPP4 negative expression,respectively(χ^(2)/P=10.128/<0.001,9.670/0.003).The results of multivariate Cox regression analysis showed that GLP-1R positive expression,DPP4 positive expression,WHO grade III,and KPS score<70 in glioma tissue were independent risk factors affecting patient survival and prognosis[HR(95%CI)=2.427(1.426-4.569),1.740(1.121-2.568),2.671(1.160-6.012),1.628(1.017-2.592)].Conclusion The increased expression of GLP-1R and DPP4 in glioma tissue is an independent factor affecting the survival and prognosis of glioma patients.