Epithelial-to-mesenchymal transition–related transcription factors are up-regulated in ependymomas and correlate with a poor prognosis

摘要

Epithelial-to-mesenchymal transition (EMT) plays an important role in invasion and metastasis of various cancers including gliomas. EMT has also been linked to cancer stem cells and resistance to chemotherapy. An initial in-silico data mining in a published ependymoma (EPN) patient series (GSE21687) revealed up-regulation of EMT transcription factors in tumor samples. Furthermore, quantitative real-time polymerase chain reaction–based gene expression analysis of EMT transcription factors in 96 EPNs showed significant up-regulation ofSNAI1,SNAI2,ZEB1, andTWIST1as compared with normal brain, associated with up-regulation ofCDH2/N-cadherin and down-regulation ofCDH1/E-cadherin. Although this was observed in varying degrees in all clinicopathological-molecular subgroups of EPNs, it was most evident in supratentorial EPNs harboring fusions ofRELA(v-rel avian reticuloendotheliosis viral oncogene homolog A) gene and in posterior fossa EPNs. Immunohistochemistry performed in 60 of the above cases corroborated with gene expression patterns, and immunopositivity for Snail, Slug, Zeb1, and Twist1 was observed in 80%, 80%, 81%, and 63% of all EPNs. Immunopositivity for N-cadherin and E-cadherin was observed in 76.6% and 2% of the cases, respectively. Univariate Cox regression analysis showed that low expression ofCDH1/E-cadherin (P?=?.002) and high expression levels ofCDH2/N-cadherin (P?