A VAT1-related gene signature predicts radioresistance in gliomas.

Background: Radiotherapy is a vital postoperative adjuvant treatment for gliomas. However, radioresistance seriously affect the treatment efficacy. Excavating the feature of radioresisrtance in gliomas comprehensively are necessary.

Methods: In the training set, 191 patients from the Chinese Glioma Genome Atlas (CGGA) were included, of which all patients had received postoperative radiotherapy. The epidemiological data and RNA sequencing data of 430 patients with whole grade glioma were obtained from the Cancer Genome Atlas (TCGA), which was used for validation.

Results: Based on the Lasso regression analysis, five-gene signature was established which was associated with VAT1-related radioresistance in gliomas. High-risk patients showed higher proportion of elders, high-grade glioma, oligodendroglial histology and IDH wild type. The risk score was identified as an independent prognostic factor in the CGGA dataset, and the high-risk score impaired the overall survival time. The biological processes of positively expressed genes of risk score were functionally involved in inflammatory and immune response. And the activation of signaling pathways in high-risk score group also showed close correlation with tumor occurrence, progression and immune microenvironment. What's more, the immune cell infiltration analysis showed that high-risk score indicated decreased CD8⁺ T cell and the upregulation of the immune checkpoints, which probably promoted the immunosuppressive microenvironment.

Conclusion: The five-gene signature can predict the survival of patients with glioma received postoperative radiotherapy efficiently. The immunosuppressive microenvironment, as a feature of glioma, potentially devote to the radioresistance.