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Independent and functional validation of a multi-tumour-type proliferation signature.
Starmans, M H W; Lieuwes, N G; Span, P N; Haider, S; Dubois, L; Nguyen, F; van Laarhoven, H W; Sweep, F C G J; Wouters, B G; Boutros, P C; Lambin, P.
Afiliação
  • Starmans MH; Department of Radiation Oncology (Maastro), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Universiteitssingel 50/23, PO box 616, 6200 MD Maastricht, The Netherlands. maud.starmans@maastrichtuniversity.nl
Br J Cancer ; 107(3): 508-15, 2012 Jul 24.
Article em En | MEDLINE | ID: mdl-22722312
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<0.001, n=1820) and NSCLC adenocarcinoma (HR=1.64, P<0.001, n=639) microarray data sets. Lastly, qPCR in a node-negative, non-adjuvantly treated breast cancer cohort (n=129) showed that patients assigned to the high-proliferation group had worse disease-free survival (HR=2.25, P<0.05).

CONCLUSION:

We have developed and validated a qPCR-based proliferation signature. This test might be used in the clinic to select (early-stage) patients for specific treatments that target proliferation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Br J Cancer Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: Br J Cancer Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Holanda