Expression of HLA-DR genes in gliomas: correlation with clinicopathological features and prognosis

Abstract

Abstract Background Human leukocyte antigen (HLA)-DR is a classical major histocompatibility complex (MHC) class II molecule encoded by five genes: HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4 and HLA-DRB5. The current study aimed to investigate the role of these genes in gliomas by analyzing microarray data. Methods We enrolled 305 patients with histologically confirmed gliomas, and performed microarray data analysis along with studying their clinical characteristics. A new variable, termed HLA-DR score, was defined to explain the expression information of all five HLA-DR genes by factor analysis. HLA-DR scores in each grade of glioma and normal brain tissue were compared using one-way ANOVA. Lastly, correlations of HLA-DR scores with progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier and Cox analysis. Results Our study indicated that an increased HLA-DR score, i.e. overexpression of HLA-DR genes, was correlated with a more aggressive glioma tumor grade (p < 0.001, One-way ANOVA). Moreover, the HLA-DR score was significantly higher in astrocytic tumors than oligodendroglial tumors (−0.718 ± 3.177 versus −2.975 ± 2.662, t-test) in low-grade gliomas (LGGs). Kaplan-Meier analysis of both PFS (p = 0.046, log-rank test; p = 0.021, Breslow test) and OS (p = 0.029, Breslow test) showed significant differences in the clinical outcomes between LGG patients with high versus low HLA-DR scores. Finally, the HLA-DR score was further identified to be an independent prognostic factor of clinical outcomes by multivariate analysis (p = 0.042 and p = 0.025, for PFS and OS, respectively) in LGG patients. Conclusion Expression of HLA-DR genes can be used to predict the tumor grade in gliomas, and the histological subtype in LGG. Furthermore, they are also an independent predictor for LGG patient survival.

Keywords

• Glioma
• Human leukocyte antigen-DR
• Prognosis