Abstract
High grade gliomas, including glioblastoma (GB), are devastating malignancies with very poor prognosis. Over the course of the last decade, there has been a failure to develop new treatments for GB. Reasons for this failure include the lack of validation of novel molecular targets, which are often characterized in animal models and directly transposed to human trials. Here we build on our previous findings, which describe how the multi-functional co-receptor Neuropilin-1 (NRP1) signals through glioma associated microglia/macrophages (GAMS) to promote murine glioma, and investigate NRP1 expression in human glioma. Clinical and gene expression data were obtained via The Cancer Genome Atlas (TCGA), and analyzed using R statistical software. Additionally, CIBERSORT in silico deconvolution was used to determine fractions of immune cell sub-populations within the gene expression datasets. We find that NRP1 expression is correlated with poor prognosis, glioma grade, and associates with the mesenchymal GB subtype. In human GB, NRP1 expression is highly correlated with markers of monocytes/macrophages, as well as genes that contribute to the pro-tumorigenic phenotype of these cells.
Highlights
Gliomas account for 60% of all primary and other CNS tumor diagnoses, and make up ~80% of all malignant brain tumors [1]
We describe here our analysis of two questions: 1) Is NRP1 expression correlated with glioma prognosis and 2) Can NRP1 expression be linked to pro-tumorigenic glioma associated microglia and macrophages (GAMs) of the tumor microenvironment (TME)
NRP1 expression correlates with poor prognosis and clinicopathological features in glioma
Summary
Gliomas account for 60% of all primary and other CNS tumor diagnoses, and make up ~80% of all malignant brain tumors [1]. The World Health Organization (WHO) classifies gliomas by histology and molecular subtype, and on a grading scale of I, II, III, IV. Glioblastoma (GB) is a grade IV glioma subtype which often spontaneously arises in the CNS, but can progress from LGG [2]. GB represents a staggering 50% of all malignant brain tumors, making it the most common adult CNS malignancy [1, 3]. The high failure rate of phase III interventional clinical trials for GB highlights concerns with the predictive power of animal models, as well as the rapid development of resistance supported by the evolving neoplasm. To aid in the development of future therapeutics for GB, novel molecular targets need to be fully validated and established
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