ИСТИНА

The integrated analysis of the glioma transcriptome may provide several novel insights into molecular heterogeneity and pathogenesis of glial tumors. We performed a systematic analysis of the intrinsic organization of complex glioma transcriptome. Gene coexpression relationships were explored in 790 glioma samples from 5 published patient cohorts treated at different institutions. We identified 20 coexpression modules that were common to all the data sets and associated with proliferation, angiogenesis, hypoxia, immune response, genomic alterations, cell differentiation phenotypes, and other features inherent to glial tumors. Individual modules were found to be organized into higher order coexpression groups, the 2 largest of them associated with glioblastoma and oligodendroglioma, respectively. A prognostic gene expression signature (185 genes) linked to a proastrocytic pattern of tumor cell differentiation was identified. This "proastrocytic" signature was associated with long survival and defined a subgroup of the previously established "proneural" class of gliomas. A strong negative correlation between proastrocytic and proneural markers across differentiated tumors underscored the distinction between these subtypes of glioma. Gliomas are primary brain tumors with high mortality and heterogeneous biology that is insufficiently understood. Role of coexpression network analysis of transcriptome in understanding of glioma biology is discussed.