Molecular and clinical characterization of PD-L1 expression at transcriptional level via 976 samples of brain glioma

Abstract

Background: PD-L1 has been widely reported as immune check points in a range of malignancies as well as some immune-originated diseases. In glioma, the role of PD-L1 remains unclear. We aimed at investigating its role at transcriptome level and relationship with clinical practice.Method and patients: In total, 976 glioma samples with transcriptome data, including 301 microarray data from Chinese Glioma Genome Atlas (CGGA project) and 675 RNAseq data from TCGA project, were enrolled into our study. Clinical and IDH mutation data were also available. R language was used as the main tool for statistical analysis and graphical work.Results: PD-L1 expression was found to be positively correlated with WHO grade of glioma. PD-L1 seemed to express more in mesenchymal subtype according to TCGA transcriptional classification scheme and may contribute as a potential marker for mesenchymal subtype in glioblastoma. Pearson correlation test indicated that PD-L1 showed robust correlation with PD1, PD-L2, and CD80 in CGGA dataset. Subsequent gene ontology analysis based on significantly correlated genes of PD-L1 revealed that PD-L1 seemed to be profoundly associated with T cell activation. To further investigate the relationship between PD-L1 expression and immune response, we selected a series of immune signatures, which were then transformed into metagenes, and found that PD-L1 expression was particularly paralleled with T-cells and macrophages-related immune response instead of B cell linage-related immune response. In line with the corresponding biological process, PD-L1 exhibited predictive value for glioma patients: Higher PD-L1 indicated significantly shorter survival, especially in glioblastoma.Conclusion: PD-L1 is upregulated in glioblastoma, and is synergistic with other check point members. Moreover, PD-L1 is significantly associated with T-cell activation and macrophage-related immune response and predicts much worse survival for patients, warranting clinical trials of PD1/PD-L1 checkpoint inhibitors for potential glioma treatment.

Genetic and clinical characterization of B7‐H3 (CD276) expression and epigenetic regulation in diffuse brain glioma

“…Similar to most immune checkpoints, B7‐H3 expression was significantly upregulated along with tumor grade, suggesting the dysregulation of immune response in higher‐grade gliomas. In molecular subtypes, we also discovered a similar expression pattern of B7‐H3 to PD‐L1, which was described in our previous study . Moreover, the ROC curve indicated that B7‐H3 can serve as a marker for mesenchymal subtype, reflecting the most profound inflammatory response in mesenchymal subtype tumors.…”

“…Accumulating evidence indicates that key components of immune response are significantly altered in gliomas, which subsequently leads to the evasion of immune surveillance of tumor cells . Immune checkpoints are thought to play a critical role in tumor immune escape . The dysregulation of immune checkpoints has attracted the attention of numerous scientific researchers and drug companies who have sought to develop inhibitors against these immune checkpoints in the tumor environment.…”

Characterization of transcriptome profile and clinical features of a novel immunotherapy target CD204 in diffuse glioma

“…CD204 was positively correlated with the protein tyrosine kinases HCK and LCK and with MHC‐I, but negatively correlated with interferon and IgG in the CGGA (Figure A and ) and TCGA datasets (Figure A and B). Additionally, CD204 was highly correlated with the immune checkpoint regulators PD‐L1 and TIM‐3 in gliomas …”

Molecular characterization of lung adenocarcinoma: A potential four–long noncoding RNA prognostic signature

“…To explore the biometric features of LUAD with lncRNAs in lncRNA signature, we identified the genes that highly related with these above lncRNAs (Pearson | R | > 0.5) in TCGA database …”