154 Drug response database with PDX tumor models in biomarker-driven multi-drug multi-arm clinical trial settings

Abstract

also been analyzed. All samples used for histopathological examination were fixed in neutral-buffered formalin, embedded in paraffin, sectioned and stained with hematoxylin-eosin. The immunohistochemical study was performed on paraffin-embedded sections using the avidin–biotin peroxidase method. To evaluate EGFR gene status, dual-color FISH analysis was performed on paraffin tissue arrays from 30 samples. Epigenetic analysis study of miRNAs and mRNA in 30 samples was performed using miRNA and mRNA Genechip Array (Affymetrix, Santa Clara, CA, USA). Expression levels of the selected miRNA (mir-200c) and mRNAs (CDH1, EGFR and ZEB1) were quantified using real-time reverse transcription-PCR (RT-PCR) analysis. MirRNA-200c showed a very significant difference between tumors having or not EGFR amplification. With respect to EGFR status our cases were categorized into three groups: high level EGFR amplification, low level EGFR amplification, and no EGFR amplification. Our results showed that microRNA-200c and E-cadherin expression are down-regulated, while ZEB1 is up-regulated, when tumors showed a high level of EGFR amplification. Conversely, ZEB1 mRNA expression levels were significantly lower in the group of tumors without EGFR amplification. Tumors with a low level of EGFR amplification showed ZEB1 expression levels comparable to those detected in the group with a high level of amplification. In this study we provide what is to our knowledge the first report of association between mirRNA-200c and EGFR amplification in glioblastomas. The mirRNA-200c plays an important role in epithelial–mesenchymal transition, but its implication in the behavior of glioblastoma is largely unknown, and we suggest that microRNA-200c may act as a potential regulator of glioblastoma migration and invasion by targeting ZEB1 mRNA.