Objective Gliomas are the most frequent intracranial tumors in adults,a better understanding on the mechanisms of glioma-mediated immune suppression can help us to develop more selective and effective cancer treatments,i.e.immunotherapies.HLA molecules are well-known for their major roles in the modulation of human immune system,and aberrant expression of HLA molecules has been indicated in multiple types of human cancers.Human leukocyte antigen-E(HLA-E)is a representative molecules of MHC class Ib(nonclassical),and has been extensively investigated in various human cancers including glioma.However,the clinical significance of HLA-E expression in glioma patients has not been elucidated.The current study aimed to investigate the association of HLA-E expression with clinicopathological features and survival in patients with diffuse glioma.Methods The data from 305 consecutive patients treated for diffuse glioma at the Glioma Center of Beijing Tiantan Hospital between June 2007 and September 2013 were retrospectively reviewed.After excluding 44 patients with secondary/recurrent tumors,261 patients with histologically confirmed primary diffuse gliomas were eventually enrolled in the study.Clinical information(age,gender,etc.),mRNA microarray and follow-up data of all patients were collected from the Chinese Glioma Genome Atlas database.Stastical analysis was conducted to identify the relationship of HLA-E with clinicopathological features and patient survival.Results A significant positive correlation of HLA-E expression and tumor grade was identified,HLA-E gene was highly overexpressed in glioblastomas(GBM,0.286 ± 0.787),followed by anaplastic gliomas(AG,0.176 ± 0.824)and low-grade gliomas(LGGs,-0.340 ± 0.802).Even in LGGs,the expression of HLA-E was significantly higher than it in normal brain tissues(-0.340 ± 0.802 versus-0.863 ± 0.228,p = 0.002,t-test).Significant differences in HLA-E expression could be observed between low-grade and high-grade glioma tissues(p = 0.001 and p < 0.001,t-test,LGGs versus AGs and LGGs versus GBMs,respectively),while no significant difference in HLA-E expression was identified between AGs and GBMs(p = 0.477,t-test).Moreover,HLA-E expression was significantly higher in diffuse astrocytomas than oligodendrogliomas(p = 0.032,ttest).Kaplan-Meier analysis showed that progression-free survival(PFS)and overall survival(OS)were significantly better in LGG patients with low HLA-E expression(p = 0.018 for PFS and p = 0.020 for OS,Log-rank test).In contrast,no significant differences were observed with respect to either PFS or OS between patients with low and high HLA-E expression in patients with AGs or GBMs.Furthermore,HLA-E expression was identified to be an independent prognostic factor by Cox analysis(p = 0.020 for PFS and p = 0.024 for OS).Conclusions In the current study,by analyzing mRNA expression microarray data of 261 patients with diffuse gliomas,the correlations of HLA-E expression with tumor grade and histological type in diffuse glioma were identified.Moreover,HLA-E expression was found to be negatively related to clinical outcomes and could serve as an independent prognostic factor in patients with LGGs.Further investigation into the roles of HLA-E and other HLA molecules in glioma can help us to obtain a better understanding of the interaction between glioma and the immune system and promote the development of relevant immunotherapy.