Identifying Diffuse Glioma Subtypes Based on Pathway Enrichment Evaluation

AbstractGliomas are highly heterogeneous in molecular, histology, and microenvironment. However, a classification of gliomas by integrating different tumor microenvironment (TME) components remains unexplored.  Based on the enrichment scores of 17 pathways involved in immune, stromal, DNA repair, and nervous system signatures in diffuse gliomas, we performed consensus clustering to uncover novel subtypes of gliomas. Consistently in three glioma datasets (TCGA-glioma, CGGA325, and CGGA301), we identified three subtypes: Stromal-enriched (Str-G), Nerve-enriched (Ner-G), and mixed (Mix-G). Ner-G was charactered by low immune infiltration levels, stromal contents, tumor mutation burden, copy number alterations, DNA repair activity, cell proliferation, epithelial-mesenchymal transformation, stemness, in tratumor heterogeneity, androgen receptor expression andEGFR,PTEN,NF1 andMUC16 mutation rates, while high enrichment of neurons and nervous system pathways, and high tumor purity, estrogen receptor expression,IDH1 andCIC mutation rates, temozolomide response rate and overall and disease-free survival rates. In contrast, Str-G displayed contrastive characteristics to Ner-G. Our analysis indicates that the heterogeneity between glioma cells and neurons is lower than that between glioma cells and immune and stromal cells. Furthermore, the abundance of neurons is positively associated with clinical outcomes in gliomas, while the enrichment of immune and stromal cells has a negative a...
Source: Interdisciplinary Sciences, Computational Life Sciences - Category: Bioinformatics Source Type: research