Abstract
Abstract Background We previously identified a precise stage-associated gene expression signature of coordinately expressed genes, including the transcription factor Slug (SNAI2) and other epithelial mesenchymal transition (EMT) markers, present in samples from publicly available gene expression datasets in multiple cancer types. The expression levels of the co-expressed genes vary in a continuous and coordinate manner across the samples, ranging from absence of expression to strong co-expression of all genes. These data suggest that tumor cells may pass through an EMT like process of mesenchymal transition to varying degrees.Findings Here we show that this signature in glioblastoma multiforme (GBM) is associated with time to recurrence following initial treatment. By analyzing data from The Cancer Genome Atlas (TCGA), we found that GBM patients who responded to therapy and had long time to recurrence had low levels of the signature in their tumor samples (P = 3x10^-7^). We also found that the signature is strongly correlated in gliomas with the putative stem cell marker CD44, and is highly enriched among the differentially expressed genes in glioblastomas vs. lower grade gliomas. Conclusions Our results suggest that long delay before tumor recurrence is associated with absence of the mesenchymal transition signature, raising the possibility that inhibiting this transition might improve the durability of therapy in glioma patients.
Highlights
We previously identified a precise stage-associated gene expression signature of coordinately expressed genes, including the transcription factor Slug (SNAI2) and other epithelial-mesenchymal transition (EMT) markers, present in samples from publicly available gene expression datasets in multiple cancer types
The expression level of the co-expressed genes varies in a continuous manner across the samples
After doing exhaustive search among all 12,042 genes, the top ranked gene (EFEMP2) had rank sum equal to 75, still worse than that (70) of the metagene. These results suggest that the signature identified in [1] comprises a synergistic collection of genes corresponding to a biological mechanism of mesenchymal transition, which, when absent, is associated with increased time period to tumor recurrence in glioblastoma multiforme (GBM)
Summary
We previously identified a precise stage-associated gene expression signature of coordinately expressed genes, including the transcription factor Slug (SNAI2) and other epithelial-mesenchymal transition (EMT) markers, present in samples from publicly available gene expression datasets in multiple cancer types. This rank sum can be used as a measure of the association of the lack of expression of a gene with the “Days to Tumor Recurrence” phenotype.
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