title: A multi-cancer mesenchymal transition gene expression signature is associated with prolonged time to recurrence in glioblastoma.
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 and had long time to recurrence had low levels of the signature in their tumor samples (P = 3×10(-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.
authors.affiliation: Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, United States of America.
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Cheng
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Kandel
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Yamashiro
authors.forename: Peter
authors.initials: P
authors.lastname: Canoll
authors.forename: Dimitris
authors.initials: D
authors.lastname: Anastassiou
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000517:prevention & control*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D030541:Databases, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005809:Genes, Regulator; D005909:Glioblastoma / Q000235:genetics / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D012008:Recurrence; D000071250:Snail Family Transcription Factors; D016019:Survival Analysis; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors