Background:

Tumor-infiltrating immune cells (TIICs), which play a pivotal role in the tumor microenvironment, are intimately related to tumor progression and clinical outcome. It remains unclear which factors influence tumor immune infiltration in lower-grade gliomas (LGGs). TEAD4 (TEA Domain Transcription Factor 4) is an essential member of the Hippo pathway that is involved in cancer progression, epithelial-mesenchymal transition, metastasis, and cancer stem cell function across multiple types of cancers. However, the prognostic value of TEAD4 and its association with TIICs in LGG have been hardly studied.

Methods:

: LGG data were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). TEAD4 expression between different groups was compared by R and survival analysis was implemented by Kaplan–Meier curves. In Virto experiments were conducted to investigate the role of TEAD4 in glioma cells. Gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network were used to investigate the differential biological processes and signaling pathways. Multiple computational methods were employed to estimate the association between TEAD4 expression and tumor microenvironment in LGG. Correlations were analyzed by Spearman correlation

Results:

: TEAD4 expression was up-regulated in higher-grade gliomas and correlated with a poorer clinical outcome. Glioma cell proliferation and migration were promoted by TEAD4 overexpression. GSEA and PPI network indicated that multiple immune-related pathways and hub genes were closely associated with TEAD4 expression in LGG specimens. TEAD4 expression was negatively associated with glioma purity. Multivariate Cox regression analysis indicated that TEAD4 expression and tumor purity were independent prognostic factors in LGG. TEAD4 expression was positively correlated with the infiltration of multiple immune cells, including plasma cells, CD8+ T cells, and macrophages M1 and M2. Correlation analysis showed that the TEAD4 level can predict the efficacy of immune checkpoint blockade therapy.

Conclusions:

: TEAD4 is highly related to glioma malignancy grades and multiple immune cell infiltration, suggesting TEAD4 can serve as a new biomarker for anti-cancer therapies in LGG.