Exon-array profiling unlocks clinically and biologically relevant gene signatures from formalin-fixed paraffin-embedded tumour samples

J. S. Hall, H. S. Leong, L. S C Armenoult, G. E. Newton, H. R. Valentine, J. J. Irlam, C. Möller-Levet, K. A. Sikand, S. D. Pepper, C. J. Miller, C. M L West

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background:Degradation and chemical modification of RNA in formalin-fixed paraffin-embedded (FFPE) samples hamper their use in expression profiling studies. This study aimed to show that useful information can be obtained by Exon-array profiling archival FFPE tumour samples.Methods:Nineteen cervical squamous cell carcinoma (SCC) and 9 adenocarcinoma (AC) FFPE samples (10-16-year-old) were profiled using Affymetrix Exon arrays. The gene signature derived was tested on a fresh-frozen non-small cell lung cancer (NSCLC) series. Exploration of biological networks involved gene set enrichment analysis (GSEA). Differential gene expression was confirmed using Quantigene, a multiplex bead-based alternative to qRT-PCR.Results:In all, 1062 genes were higher in SCC vs AC, and 155 genes higher in AC. The 1217-gene signature correctly separated 58 NSCLC into SCC and AC. A gene network centered on hepatic nuclear factor and GATA6 was identified in AC, suggesting a role in glandular cell differentiation of the cervix. Quantigene analysis of the top 26 differentially expressed genes correctly partitioned cervix samples as SCC or AC.Conclusion:FFPE samples can be profiled using Exon arrays to derive gene expression signatures that are sufficiently robust to be applied to independent data sets, identify novel biology and design assays for independent platform validation. © 2011 Cancer Research UK All rights reserved.
    Original languageEnglish
    Pages (from-to)971-981
    Number of pages10
    JournalBritish Journal of Cancer
    Volume104
    Issue number6
    DOIs
    Publication statusPublished - 15 Mar 2011

    Keywords

    • cervix cancer
    • exon array
    • expression profiling
    • FFPE
    • histology

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