A Multi-Cancer Mesenchymal Transition Gene Expression Signature Is Associated with Prolonged Time to Recurrence in GlioblastomaReport as inadecuate




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A stage-associated gene expression signature of coordinately expressed genes, including the transcription factor Slug SNAI2 and other epithelial-mesenchymal transition EMT markers has been found present in samples from publicly available gene expression datasets in multiple cancer types, including nonepithelial cancers. 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. Here we show that, in glioblastoma multiforme GBM, this signature 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 Pā€Š=ā€Š3Ɨ10āˆ’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. 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.



Author: Wei-Yi Cheng, Jessica J. Kandel, Darrell J. Yamashiro, Peter Canoll, Dimitris Anastassiou

Source: http://plos.srce.hr/



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