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

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.

A novel Foxp3-related immune prognostic signature for glioblastoma multiforme based on immunogenomic profiling

“…Ninety-one differentially expressed immune genes (DEIGs) were then selected using the ImmPort database [ 18 ] ( Figure 3A , 3B ). The DEIGs were uploaded to the Metascape website to identify Gene Ontology (GO) Terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.…”

“…Genes with log2 |fold change| ≥1 and False Discovery Rate (FDR) <0.05 were selected as differentially expressed genes (DEGs). DEIGs were identified by the ImmPort database ( https://www.immport.org/ ) [ 18 ].…”

Predictive Evaluation of Quantitative Spatial Profiling of the Tumor Microenvironment by Multiplex Immunofluorescence in Recurrent Glioblastoma Treated with PD-1 Inhibitors

“…We also found that a) PD-1/PD-L1 interaction score may be a predictor of OS in recurrent GBM patients who received anti-PD-1 therapy, b) HLA-DR is associated with worse OS in recurrent GBM patients who received anti-PD-1 therapy, and c) the coexpression of PTEN loss and Ki67+ tumor and non-tumor cells may provide a more speci c marker of immunosuppression in the GBM microenvironment. HLA-DR is a generic, non-speci c biomarker in GBM; however, Fan et al prove that an increased HLA-DR score was correlated with a more aggressive glioma tumor grade [17]. Additionally, they investigated whether HLA-DR scores predicted survival in GBM patients treated with immunotherapy but found no signi cant difference in the prognosis of subgroups with high and low HLA-DR scores.…”

Predictive evaluation of quantitative spatial profiling of the tumor microenvironment by multiplex immunofluorescence in recurrent glioblastoma treated with PD-1 inhibitors.

“…HLA-DR is a generic, non-speci c biomarker in GBM; however, Fan et al prove that an increased HLA-DR score was correlated with a more aggressive glioma tumor grade [17]. Additionally, they investigated whether HLA-DR scores predicted survival in GBM patients treated with immunotherapy but found no signi cant difference in the prognosis of subgroups with high and low HLA-DR scores.…”