MR1 Overexpression Correlates with Poor Clinical Prognosis in Glioma Patients

Background: Glioblastoma is the most common adult primary brain tumor with near-universal fatality. Major histocompatibility complex (MHC) class I molecules are important mediators of CD8 activation and can be downregulated by cancer cells to escape immune surveillance. MR1 is a nonclassical MHC-I-like molecule responsible for the activation of a subset of T cells. Although high levels of MR1 expression should enhance cancer cell recognition, various tumors demonstrate MR1 overexpression with unknown implications. Here, we study the role of MR1 in glioma.

Methods: Using multi-omics data from the Cancer Genome Atlas (TCGA), we studied expression patterns and its impact on survival for various solid tumors. In glioma specifically, we validated expression by histology, elucidate transcriptomic profiles of high versus low gliomas. To understand expression, we analyzed the methylation status of the gene and gene-related transcription factor (TF) expression.

Results: is overexpressed in all grades of glioma and many other solid cancers. However, only in glioma, overexpression correlated with poor overall survival and demonstrated global dysregulation of many immune-related genes in an -dependent manner. MR1 overexpression correlated with decreased gene methylation and upregulation of predicted promoter binding TFs, implying gene methylation might regulate MR1 expression in glioma.

Conclusions: Our in silico analysis shows that expression is a predictor of clinical outcome in glioma patients and is potentially regulated at the epigenetic level, resulting in immune-related genes dysregulation. These findings need to be validated using independent in vitro and in vivo functional studies.