Independent and functional validation of a multi-tumour-type proliferation signature

M. H. W. Starmans; N. G. Lieuwes; P. N. Span; S. Haider; L. Dubois; F. Nguyen; H. W. van Laarhoven; F. C. G. J. Sweep; B. G. Wouters; P. C. Boutros; P. Lambin

doi:10.1038/bjc.2012.269

Independent and functional validation of a multi-tumour-type proliferation signature

M. H. W. Starmans^*, N. G. Lieuwes, P. N. Span, S. Haider, L. Dubois, F. Nguyen, H. W. van Laarhoven, F. C. G. J. Sweep, B. G. Wouters, P. C. Boutros, P. Lambin

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

9 Citations (Web of Science)

Abstract

BACKGROUND: Previously we demonstrated that an mRNA signature reflecting cellular proliferation had strong prognostic value. As clinical applicability of signatures can be controversial, we sought to improve our marker's clinical utility by validating its biological relevance, reproducibility in independent data sets and applicability using an independent technique. METHODS: To facilitate signature evaluation with quantitative PCR (qPCR) a novel computational procedure was used to reduce the number of signature genes without significant information loss. These genes were validated in different human cancer cell lines upon serum starvation and in a 168 xenografts panel. Analyses were then extended to breast cancer and non-small-cell lung cancer (NSCLC) patient cohorts. RESULTS: Expression of the qPCR-based signature was dramatically decreased under starvation conditions and inversely correlated with tumour volume doubling time in xenografts. The signature validated in breast cancer (hazard ratio (HR) = 1.63, P

Original language	English
Pages (from-to)	508-515
Journal	British Journal of Cancer
Volume	107
Issue number	3
DOIs	https://doi.org/10.1038/bjc.2012.269
Publication status	Published - 24 Jul 2012

Keywords

biomarkers
gene expression microarray
statistical analysis
prognosis
proliferation

Access to Document

10.1038/bjc.2012.269Licence: CC BY

Cite this

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title = "Independent and functional validation of a multi-tumour-type proliferation signature",

abstract = "BACKGROUND: Previously we demonstrated that an mRNA signature reflecting cellular proliferation had strong prognostic value. As clinical applicability of signatures can be controversial, we sought to improve our marker's clinical utility by validating its biological relevance, reproducibility in independent data sets and applicability using an independent technique. METHODS: To facilitate signature evaluation with quantitative PCR (qPCR) a novel computational procedure was used to reduce the number of signature genes without significant information loss. These genes were validated in different human cancer cell lines upon serum starvation and in a 168 xenografts panel. Analyses were then extended to breast cancer and non-small-cell lung cancer (NSCLC) patient cohorts. RESULTS: Expression of the qPCR-based signature was dramatically decreased under starvation conditions and inversely correlated with tumour volume doubling time in xenografts. The signature validated in breast cancer (hazard ratio (HR) = 1.63, P",

keywords = "biomarkers, gene expression microarray, statistical analysis, prognosis, proliferation",

author = "Starmans, {M. H. W.} and Lieuwes, {N. G.} and Span, {P. N.} and S. Haider and L. Dubois and F. Nguyen and {van Laarhoven}, {H. W.} and Sweep, {F. C. G. J.} and Wouters, {B. G.} and Boutros, {P. C.} and P. Lambin",

year = "2012",

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doi = "10.1038/bjc.2012.269",

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T1 - Independent and functional validation of a multi-tumour-type proliferation signature

AU - Starmans, M. H. W.

AU - Lieuwes, N. G.

AU - Span, P. N.

AU - Haider, S.

AU - Dubois, L.

AU - Nguyen, F.

AU - van Laarhoven, H. W.

AU - Sweep, F. C. G. J.

AU - Wouters, B. G.

AU - Boutros, P. C.

AU - Lambin, P.

PY - 2012/7/24

Y1 - 2012/7/24

N2 - BACKGROUND: Previously we demonstrated that an mRNA signature reflecting cellular proliferation had strong prognostic value. As clinical applicability of signatures can be controversial, we sought to improve our marker's clinical utility by validating its biological relevance, reproducibility in independent data sets and applicability using an independent technique. METHODS: To facilitate signature evaluation with quantitative PCR (qPCR) a novel computational procedure was used to reduce the number of signature genes without significant information loss. These genes were validated in different human cancer cell lines upon serum starvation and in a 168 xenografts panel. Analyses were then extended to breast cancer and non-small-cell lung cancer (NSCLC) patient cohorts. RESULTS: Expression of the qPCR-based signature was dramatically decreased under starvation conditions and inversely correlated with tumour volume doubling time in xenografts. The signature validated in breast cancer (hazard ratio (HR) = 1.63, P

AB - BACKGROUND: Previously we demonstrated that an mRNA signature reflecting cellular proliferation had strong prognostic value. As clinical applicability of signatures can be controversial, we sought to improve our marker's clinical utility by validating its biological relevance, reproducibility in independent data sets and applicability using an independent technique. METHODS: To facilitate signature evaluation with quantitative PCR (qPCR) a novel computational procedure was used to reduce the number of signature genes without significant information loss. These genes were validated in different human cancer cell lines upon serum starvation and in a 168 xenografts panel. Analyses were then extended to breast cancer and non-small-cell lung cancer (NSCLC) patient cohorts. RESULTS: Expression of the qPCR-based signature was dramatically decreased under starvation conditions and inversely correlated with tumour volume doubling time in xenografts. The signature validated in breast cancer (hazard ratio (HR) = 1.63, P

KW - biomarkers

KW - gene expression microarray

KW - statistical analysis

KW - prognosis

KW - proliferation

U2 - 10.1038/bjc.2012.269

DO - 10.1038/bjc.2012.269

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VL - 107

SP - 508

EP - 515

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

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