Transcriptome analysis reveals high tumor heterogeneity with respect to re-activation of stemness and proliferation programs

Supplementary Data Files for the paper "Transcriptome analysis reveals high tumor heterogeneity with respect to re-activation of stemness and proliferation programs" 

Abstract:
Significant alterations in signaling pathways and transcriptional regulatory programs together represent major hallmarks of many cancers. These, among all, include the reactivation of stemness, which is registered by the expression of pathways that are active in the embryonic stem cells (ESCs). Here, we assembled the gene sets that reflect the stemness and proliferation signatures and used them to analyze a large panel of RNA-seq data from The Cancer Genome Atlas (TCGA) Consortium in order to specifically assess the expression of stemness-related and proliferation-related genes across a collection of different tumor types. We introduced a metric that captures the collective similarity of the expression profile of a tumor to that of ESCs, which showed that stemness and proliferation signatures vary greatly between different tumor types. We observed a high degree of heterogeneity in the expression of stemness and proliferation-related genes not only inter-, but also intratumorally, which was independent of tumor purity and was significantly associated with hazard ratios only in a fraction of tumors. Taken together, these results indicate that the expression of stemness signatures is highly heterogeneous and cannot be used as a universal determinant of cancer.