Consistent metagenes from cancer expression profiles yield agent specific predictors of chemotherapy response

Qiyuan Li, Aron C. Eklund, Nicolai J. Birkbak, Christine Desmedt, Benjamin Haibe-Kains, Christos Sotiriou, W. Fraser Symmans, Lajos Pusztai, Søren Brunak, Andrea L. Richardson, Zoltan Szallasi

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Genome scale expression profiling of human tumor samples is likely to yield improved cancer treatment decisions. However, identification of clinically predictive or prognostic classifiers can be challenging when a large number of genes are measured in a small number of tumors.Results: We describe an unsupervised method to extract robust, consistent metagenes from multiple analogous data sets. We applied this method to expression profiles from five "double negative breast cancer" (DNBC) (not expressing ESR1 or HER2) cohorts and derived four metagenes. We assessed these metagenes in four similar but independent cohorts and found strong associations between three of the metagenes and agent-specific response to neoadjuvant therapy. Furthermore, we applied the method to ovarian and early stage lung cancer, two tumor types that lack reliable predictors of outcome, and found that the metagenes yield predictors of survival for both.Conclusions: These results suggest that the use of multiple data sets to derive potential biomarkers can filter out data set-specific noise and can increase the efficiency in identifying clinically accurate biomarkers.

Original languageEnglish (US)
Article number310
JournalBMC Bioinformatics
Volume12
DOIs
StatePublished - Jul 28 2011

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

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