Research About Clinical Significance Of PD-L1 Protein Expression And Its Correlation With VEGF In Patients With Glioma

OBJECTIVE: Glioma is derived from neuroepithelial tumors,accounting for 40-50% of primary brain tumors,is the most common intracranial malignant tumors.The annual incidence of glioma in China is 3-6 people / 10 million people,the annual death toll of 30,000 people.According to pathology can be divided into astrocytoma,medulloblastoma,glioblastoma(GBM)and so on.Although the traditional treatment methods such as surgery,radiotherapy and chemotherapy have been greatly improved in recent years,the prognosis of gliomas has not improved significantly,especially in high-grade gliomas.There is a need for a traditional approach to treatment to improve the treatment of gliomas.Programmed cell death-ligand 1(PD-L1)belongs to the B7 family of co-inhibitory molecules,the activation and tolerance of cells play a key regulatory role.Blocking PD-L1 or its receptor PD-1 helps to restore the body’s anti-tumor immune response.Tumor angiogenesis plays an important role in the growth and metastasis of gliomas,in which vascular endothelial growth factor(VEGF)is one of the important factors of tumor angiogenesis.This study focused on the clinical significance of PD-L1 protein expression in patients with glioma and its relationship with VEGF;In addition,we conducted a meta-analysis to determine the predictive value of PD-L1 in patients with gliomas;we expect to provide a potentially viable therapeutic strategy in glioma.METHODS: 1.Data for 64 patients with primary glioma recorded from June 2007 to December 2013 were immunohistochemically evaluated for the expressions of PD-L1 and VEGF.The clinical data of patients were collected.2.The relationship between PD-L1 expression with clinicopathological parameters and prognosis of glioma was analyzed.3.Pro Plus software was used to quantify the mean optical density(MOD)of the immunohistochemical image.Analysis of the relationship between PD-L1 and VEGF.4.Electronic databases were searched to identify studies that evaluated PD-L1 expression and overall survival(OS)in patients with glioma.RESULTS: 1.PD-L1 expression was detected not only on the cell surface but also in the cytoplasm.PD-L1 protein expression was examined in 64 glioma tissues.50 of 64 glioma tissues(78.12%)showed varied degrees of PD-L1 expression.2.No significant associations wee found between PD-L1 expression and Other clinicopathological parameters such as gender,age and KPS.PD-L1 protein expression was associated with pathological grade and VEGF.3.The median survival time of patients with PD-L1 positive expression(526 days)was significantly lower than that of patients with negative expression(2270 days)(P=0.016).Multivariate Cox regression analysis showed that PD-L1 positive(HR=6.153,90%CI: 1.55-24.34,P=0.010)and ages≥60(HR=5.662,90%CI: 2.264-14.16,P=0.001)were independent prognostic factors for patients with gliomas.4.The mean MOD of PD-L1 in high-grade group(0.1144±0.02754)was greater than that in low-grade group(0.005129±0.001441)5.There was a significant positive correlation between PD-L1 with VEGF(r=0.314,P=0.011).6.A total of 6 studies(published in 4 articles)that involved 1052 patients were included in this meta-analysis.The pooled results showed that positive PD-L1 expression was associated with worse OS in glioma patients(HR=1.30,95% CI: 1.02-1.65,p=0.032).CONCLUSIONS: PD-L1 protein is highly expressed in gliomas and is associated with tumor malignancy and VEGF expression.PD-L1 may be a promising biomarker that predicts disease progression in patients with gliomas or GBM.PD-L1 may play an important role in the occurrence and development process of glioma.In order to consider the application of anti-PD-L1 combined with VEGF anti-angiogenesis for the treatment of human glioma provides a therapeutic strategy.