Epithelial-mesenchymal transition-related gene expression as a new prognostic marker for neuroblastoma

Abstract

Neuroblastoma (NB) is a highly metastatic tumor in children. The epithelial-mesenchymal transition (EMT) is an important mechanism for both the initiation of tumor invasion and subsequent metastasis. This study investigated the role of EMT in the progression of NB. Using EMT assays on samples from 11 tumors, we identified 14 genes that were either differentially expressed between tumors of different stages or highly upregulated in NB. Quantitative RT-PCR of these genes was conducted in 96 NB tumors and their expression levels were compared between stages and between tumors with the presence and absence of MYCN amplification. The association of survival rate with differential gene expression was investigated. Expression of KRT19 was significantly decreased in stage 3 or 4 NB as well as stage 4S NB compared with stage 1 or 2 NB. Expression levels of KRT19 and ERBB3 were significantly low, and expression levels of TWST1 and TCF3 were high in MYCN-amplified NB. The patients with low expression of KRT19 or ERBB3 showed significantly worse overall survival. Furthermore, the correlation between high invasive ability and low expression of KRT19 and ERBB3 was suggested in vitro using six NB cell lines. The authors conclude that downregulation of KRT19 is highly associated with tumor progression in NB and metastasis in localized primary NB and that low expression of ERBB3 is also associated with progression of NB.