Roles of Tenascin-XB in the Glioma Immune Microenvironment

Abstract

Background: Previous studies have reported the critical roles of tumor cells and the tumor microenvironment in tumor prognosis and immunotherapeutic response. However, how Tenascin-XB (TNXB) expression relates to glioma prognosis and to the levels of tumor-infiltrating immune cells in various cancers has remained elusive. Therefore, this work aimed to investigate the expression, prognostic value, biological function and correlation between TNXB expression and the levels of tumor-infiltrating immune cells in glioma tissues.Methods: First, we explored TNXB expression in glioma tissues by using online biological databases. Second, we assessed the clinical importance of TNXB expression with chi-squared tests, Cox regression and Kaplan-Meier curve analyses. Third, we examined the relationship between TNXB expression and the levels of tumor-infiltrating immune cells in glioma tissues in an online database. Additionally, we assessed the associations of TNXB expression with genetic markers of immune cells and common immune-checkpoint molecules.Results: Elevated TNXB expression in glioma tissues correlated with tumor grade, according to several databases. Elevated TNXB expression was significantly associated with negative clinicopathological manifestations and poorer prognosis, on the basis of TCGA (n=510) data. Furthermore, univariate and multivariate Cox regression indicated that TNXB was an independent indicator of glioma prognosis. Pathway enrichment analyses suggested that TNXB participates in the immune response, humoral immune response and interferon-gamma-mediated signaling pathways. Importantly, TNXB expression was significantly associated with higher levels of tumor-infiltrating immune cells in diverse cancers. Furthermore, TNXB expression was strongly associated with genetic markers of immune cells and common immune-checkpoint molecules (e.g., PD-1, PD-L1, CTLA4, TIM-3, LAG3, PDCD1LG2, TIGIT and Siglec-15).Conclusions: TNXB expression correlates with poorer prognosis and higher levels of tumor-infiltrating immune cells in several cancers. In addition, TNXB expression is likely to contribute to the regulation of dendritic cells, exhausted T cells, regulatory T cells and tumor-associated macrophages in gliomas. Consequently, TNXB may serve as an important prognostic marker and may play an immunomodulatory role in tumors.

Transcription factor CASZ1 increases an oncogenic transcriptional process in tumorigenesis and progression of glioma cells

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Microfibrillar-associated protein 2 is a prognostic marker that correlates with the immune microenvironment in glioma

“…The visual prediction model on which these findings are based has been reported to exhibit strong predictive value ( Qu et al, 2021b ). Recent progress in sequencing technology has promoted in-depth investigations into the molecular diagnosis of gliomas, revealing several genetic biomarkers ( Hu and Qu, 2021 ; Mao et al, 2022 ). The diagnostic and prognostic value of biomarkers in glioma was confirmed, and some biomarkers were used to guide the diagnosis and treatment of glioma in the fifth edition of the classification of central nervous system tumors released by WHO in 2021 ( Louis et al, 2021 ).…”