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

doi:10.1038/bjc.2011.66

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 journal › Article › peer-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 language	English
Pages (from-to)	971-981
Number of pages	10
Journal	British Journal of Cancer
Volume	104
Issue number	6
DOIs	https://doi.org/10.1038/bjc.2011.66
Publication status	Published - 15 Mar 2011

Keywords

cervix cancer
exon array
expression profiling
FFPE
histology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/bjc.2011.66

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Hall, J. S., Leong, H. S., Armenoult, L. S. C., Newton, G. E., Valentine, H. R., Irlam, J. J., Möller-Levet, C., Sikand, K. A., Pepper, S. D., Miller, C. J., & West, C. M. L. (2011). Exon-array profiling unlocks clinically and biologically relevant gene signatures from formalin-fixed paraffin-embedded tumour samples. British Journal of Cancer, 104(6), 971-981. https://doi.org/10.1038/bjc.2011.66

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

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. {\textcopyright} 2011 Cancer Research UK All rights reserved.",

keywords = "cervix cancer, exon array, expression profiling, FFPE, histology",

author = "Hall, {J. S.} and Leong, {H. S.} and Armenoult, {L. S C} and Newton, {G. E.} and Valentine, {H. R.} and Irlam, {J. J.} and C. M{\"o}ller-Levet and Sikand, {K. A.} and Pepper, {S. D.} and Miller, {C. J.} and West, {C. M L}",

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Hall, JS, Leong, HS, Armenoult, LSC, Newton, GE, Valentine, HR, Irlam, JJ, Möller-Levet, C, Sikand, KA, Pepper, SD, Miller, CJ & West, CML 2011, 'Exon-array profiling unlocks clinically and biologically relevant gene signatures from formalin-fixed paraffin-embedded tumour samples', British Journal of Cancer, vol. 104, no. 6, pp. 971-981. https://doi.org/10.1038/bjc.2011.66

TY - JOUR

T1 - Exon-array profiling unlocks clinically and biologically relevant gene signatures from formalin-fixed paraffin-embedded tumour samples

AU - Hall, J. S.

AU - Leong, H. S.

AU - Armenoult, L. S C

AU - Newton, G. E.

AU - Valentine, H. R.

AU - Irlam, J. J.

AU - Möller-Levet, C.

AU - Sikand, K. A.

AU - Pepper, S. D.

AU - Miller, C. J.

AU - West, C. M L

PY - 2011/3/15

Y1 - 2011/3/15

N2 - 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.

AB - 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.

KW - cervix cancer

KW - exon array

KW - expression profiling

KW - FFPE

KW - histology

U2 - 10.1038/bjc.2011.66

DO - 10.1038/bjc.2011.66

M3 - Article

C2 - 21407225

VL - 104

SP - 971

EP - 981

JO - BJC

JF - BJC

SN - 0007-0920

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

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