Identification Of Immune Networks Influenced By Mir-200c In IDH1-Mutant Lower-Grade Gliomas Using WGCNA

Abstract Gliomas are the most common intracranial tumors with a highly invasive nature and poor prognosis. Different stages of gliomas have distinct alterations in genome, genetic and epigenetic changes. Here, we performed enrichment analysis and weighted gene correlation network analysis (WGCNA) on the Cancer Genome Atlas (TCGA) RNA-seq dataset to identify core genes and potential pathways involved in Isocitrate Dehydrogenase 1 (IDH1) mutant lower-grade gliomas (LGG). The IDH1-mutant LGG patients were found to frequently co-occur with abundant genetic alterations, surprisingly, the miR-200c/141 remain unchanged. Although located in close proximity, the expression level of miR-200c was more affected by methylation level and copy number variation than that of miR-141 in IDH1-mutant LGG. GO analysis indicated the high correlation between miR-200c and immune response. Gene set enrichment analysis (GSEA) suggested that leukocyte activation, inflammatory response, lymphocyte activation and adaptive immune response were significantly up-regulated in miR-200c high-expression group. Enrichment analysis demonstrated that leukocyte activation, immune response, lymphocyte proliferation, cell-cell adhesion and other items were participants in IDH1-mutant LGG samples. Furthermore, WGCNA yielded 33 significant modules, including the yellow module which contains genes involved in the immune response. Taken together, these results proposed a promising new therapeutic strategy for treating LGG gliomas through a miR-200c-mediated immune response pathway.