Abstract
Background Glioma is the most common primary intracranial tumor and is associated with poor prognosis. Identifying effective biomarkers for glioma is particularly important. MXRA5, a secreted glycoprotein, is involved in cell adhesion and extracellular matrix remodeling and has been reported to be expressed in many cancers. However, the role and mechanism of action of MXRA5 in gliomas remain unclear. This study was aimed at investigating the role of MXRA5 at the transcriptome level and its clinical prognostic value. Methods In this study, RNA microarray data of 301 glioma patients from the Chinese Glioma Genome Atlas (CGGA) were collected as a training cohort and RNA-seq data of 702 glioma samples from The Cancer Genome Atlas (TCGA) were used for validation. We analyzed the clinical and molecular characteristics as well as the prognostic value of MXRA5 in glioma. In addition, the expression level of MXRA was evaluated in 28 glioma tissue samples. Results We found that MXRA5 expression was significantly upregulated in high-grade gliomas and IDH wild-type gliomas compared to controls. Receiver operating characteristic (ROC) analysis showed that MXRA5 is a potential marker of the mesenchymal subtype of glioblastoma multiforme (GBM). We found that MXRA5 expression is highly correlated with immune checkpoint molecule expression levels and tumor-associated macrophage infiltration. High MXRA5 expression could be used as an independent indicator of poor prognosis in glioma patients. Conclusion Our study suggests that MXRA5 expression is associated with the clinicopathologic features and poor prognosis of gliomas. MXRA5 may play an important role in the immunosuppressive microenvironment of glioma. As a secreted glycoprotein, MXRA5 is a potential circulating biomarker for glioma, deserving further investigation.
Highlights
Gliomas account for the majority of primary malignant brain tumors in adults, and glioblastoma multiforme (GBM) is the most invasive and incurable type, which is characterized by a high recurrence rate and a high fatality rate [1, 2]
We found that Matrix-remodeling associated protein 5 (MXRA5) mRNA and protein expression was upregulated in glioma, especially GBM, and was an unfavorable prognostic biomarker for patients with glioma
We found that MXRA5 expression was higher in glioma than in most other cancers (Figure 1(b))
Summary
Gliomas account for the majority of primary malignant brain tumors in adults, and GBM is the most invasive and incurable type, which is characterized by a high recurrence rate and a high fatality rate [1, 2]. Matrix-remodeling associated protein 5 (MXRA5), a secreted glycoprotein, is a member of the MXRA protein family that participates in cell adhesion and extracellular matrix (ECM) remodeling [7]. This protein contains 7 leucine-rich repeats and 12 immunoglobulin-like C2-type domains related to perlecan. MXRA5, a secreted glycoprotein, is involved in cell adhesion and extracellular matrix remodeling and has been reported to be expressed in many cancers. The expression level of MXRA was evaluated in 28 glioma tissue samples. High MXRA5 expression could be used as an independent indicator of poor prognosis in glioma patients. Our study suggests that MXRA5 expression is associated with the clinicopathologic features and poor prognosis of gliomas. MXRA5 is a potential circulating biomarker for glioma, deserving further investigation
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