Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: A prospective, two-stage study

David Olmos, Daniel Brewer, Jeremy Clark, Daniel C. Danila, Chris Parker, Gerhardt Attard, Martin Fleisher, Alison H M Reid, Elena Castro, Shahneen K. Sandhu, Lorraine Barwell, Nikhil Babu Oommen, Suzanne Carreira, Charles G. Drake, Robert Jones, Colin S. Cooper, Howard I. Scher, Johann S. de Bono

Research output: Contribution to journalArticle

Abstract

Background: Biomarkers are urgently needed to dissect the heterogeneity of prostate cancer between patients to improve treatment and accelerate drug development. We analysed blood mRNA expression arrays to identify patients with metastatic castration-resistant prostate cancer with poorer outcome. Methods: Whole blood was collected into PAXgene tubes from patients with castration-resistant prostate cancer and patients with prostate cancer selected for active surveillance. In stage I (derivation set), patients with castration-resistant prostate cancer were used as cases and patients under active surveillance were used as controls. These patients were recruited from The Royal Marsden Hospital NHS Foundation Trust (Sutton, UK) and The Beatson West of Scotland Cancer Centre (Glasgow, UK). In stage II (validation-set), patients with castration-resistant prostate cancer recruited from the Memorial Sloan-Kettering Cancer Center (New York, USA) were assessed. Whole-blood RNA was hybridised to Affymetrix U133plus2 microarrays. Expression profiles were analysed with Bayesian latent process decomposition (LPD) to identify RNA expression profiles associated with castration-resistant prostate cancer subgroups; these profiles were then confirmed by quantative reverse transcriptase (qRT) PCR studies and correlated with overall survival in both the test-set and validation-set. Findings: LPD analyses of the mRNA expression data divided the evaluable patients in stage I (n=94) into four groups. All patients in LPD1 (14 of 14) and most in LPD2 (17 of 18) had castration-resistant prostate cancer. Patients with castration-resistant prostate cancer and those under active surveillance comprised LPD3 (15 of 31 castration-resistant prostate cancer) and LDP4 (12 of 21 castration-resistant prostate cancer). Patients with castration-resistant prostate cancer in the LPD1 subgroup had features associated with worse prognosis and poorer overall survival than patients with castration-resistant prostate cancer in other LPD subgroups (LPD1 overall survival 10·7 months [95% CI 4·1-17·2] vs non-LPD1 25·6 months [18·0-33·4]; p

Original languageEnglish (US)
Pages (from-to)1114-1124
Number of pages11
JournalThe Lancet Oncology
Volume13
Issue number11
DOIs
StatePublished - Nov 2012

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ASJC Scopus subject areas

  • Oncology

Cite this

Olmos, D., Brewer, D., Clark, J., Danila, D. C., Parker, C., Attard, G., Fleisher, M., Reid, A. H. M., Castro, E., Sandhu, S. K., Barwell, L., Oommen, N. B., Carreira, S., Drake, C. G., Jones, R., Cooper, C. S., Scher, H. I., & de Bono, J. S. (2012). Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: A prospective, two-stage study. The Lancet Oncology, 13(11), 1114-1124. https://doi.org/10.1016/S1470-2045(12)70372-8