a multi-cancer mesenchymal transition gene expression signature is associated with prolonged time to recurrence in glioblastomamulti-cancer间充质转变基因表达特征与长时间复发胶质母细胞瘤.pdfVIP

A Multi-Cancer Mesenchymal Transition Gene Expression Signature Is Associated with Prolonged Time to Recurrence in Glioblastoma Wei-Yi Cheng1,7, Jessica J. Kandel2,3,4, Darrell J. Yamashiro2,4,5, Peter Canoll5,6, Dimitris Anastassiou1,7* 1 Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, United States of America, 2 Institute for Cancer Genetics, Columbia University, New York, New York, United States of America, 3 Department of Surgery, Columbia University, New York, New York, United States of America, 4 Department of Pediatrics, Columbia University, New York, New York, United States of America, 5 Department of Pathology and Cell Biology, Columbia University, New York, New York, United States of America, 6 Columbia Stem Cell Initiative, Columbia University, New York, New York, United States of America, 7 Department of Electrical Engineering, Columbia University, New York, New York, United States of America Abstract 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