TEAD4 is a novel independent predictor of prognosis in LGG patients with IDH mutation

Abstract

TEA domain family members (TEADs) play important roles in tumor progression. Till now, the genomic status of TEADs in patients with glioma has not been well investigated. To confirm whether the genomic status of TEADs could affect the prognosis of patients with glioma, the copy number variation (CNV), mutation and expression data of glioma cohorts in The Cancer Genome Atlas, Gene Expression Omnibus and Chinese Glioma Genome Atlas were comprehensively analyzed. Results showed that TEAD CNV frequency in lower grade gliomas (LGGs) was higher than in glioblastoma multiforme (GBM). Multivariate cox regression analysis showed that TEAD4 CNV increase was significantly associated with overall survival (OS) and disease-free survival (DFS) in LGGs (OS p = 0.022, HR = 1.444, 95% CI: 1.054–1.978; DFS p = 0.005, HR = 1.485, 95% CI: 1.124–1.962), while not in GBM. Patients with TEAD4 CNV increase showed higher expression level of TEAD4 gene. In LGG patients with IDH mutation, those with higher TEAD4 expression levels had shorter OS and DFS. Integrating TEAD4 CNV increase, IDH mutations, TP53 mutation, ATRX mutation and 1p19q co-deletion would separate patients with LGG into four groups with significant differences in prognosis. These study results suggested that TEAD4 variations were independent predictive biomarkers for the prognosis in patients with LGG with IDH mutation.

Keywords

• low-grade glioma
• copy number variation
• tead4
• prognosis
• gene expression