Transcriptional co-expression regulatory network analysis for Snail and Slug identifies , an inflammatory cytokine receptor, to be preferentially expressed in ST-EPN- and PF-EPN-A molecular subgroups of intracranial ependymomas.

Recent molecular subgrouping of ependymomas (EPN) by DNA methylation profiling has identified ST-EPN- and PF-EPN-A subgroups to be associated with poor outcome. Snail/Slug are cardinal epithelial-to-mesenchymal transcription factors (EMT-TFs) and are overexpressed in several CNS tumors, including EPNs. A systematic analysis of gene-sets/modules co-expressed with and genes using published expression microarray dataset (GSE27279)identified 634 genes for with enriched TGF-β, PPAR and PI3K signaling pathways, and 757 genes for with enriched focal adhesion, ECM-receptor interaction and regulation of actin cytoskeleton related pathways. Of 37 genes commonly expressed with both and , , a cytokine receptor of interleukin-1 receptor family, was positively correlated with Snail (r=0.43) and Slug (r=0.51), preferentially expressed in ST-EPN- and PF-EPN-A molecular groups, and enriched for pathways related to inflammation, angiogenesis and glycolysis. expression was fairly specific to EPNs among various CNS tumors analyzed. It also showed significant positive correlation with EMT, stemness and MDSC (myeloid derived suppressor cell) markers. Our study reports as a poor prognostic marker associated with EMT-like phenotype and stemness in EPNs. Our findings emphasize the need to further examine and validate IL1R1 as a novel therapeutic target in aggressive subsets of intracranial EPNs.