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Integrated Analysis of Multiple Microarray Datasets Identifies a Reproducible Survival Predictor in Ovarian Cancer

Author

Listed:
  • Panagiotis A Konstantinopoulos
  • Stephen A Cannistra
  • Helen Fountzilas
  • Aedin Culhane
  • Kamana Pillay
  • Bo Rueda
  • Daniel Cramer
  • Michael Seiden
  • Michael Birrer
  • George Coukos
  • Lin Zhang
  • John Quackenbush
  • Dimitrios Spentzos

Abstract

Background: Public data integration may help overcome challenges in clinical implementation of microarray profiles. We integrated several ovarian cancer datasets to identify a reproducible predictor of survival. Methodology/Principal Findings: Four microarray datasets from different institutions comprising 265 advanced stage tumors were uniformly reprocessed into a single training dataset, also adjusting for inter-laboratory variation (“batch-effect”). Supervised principal component survival analysis was employed to identify prognostic models. Models were independently validated in a 61-patient cohort using a custom array genechip and a publicly available 229-array dataset. Molecular correspondence of high- and low-risk outcome groups between training and validation datasets was demonstrated using Subclass Mapping. Previously established molecular phenotypes in the 2nd validation set were correlated with high and low-risk outcome groups. Functional representational and pathway analysis was used to explore gene networks associated with high and low risk phenotypes. A 19-gene model showed optimal performance in the training set (median OS 31 and 78 months, p

Suggested Citation

  • Panagiotis A Konstantinopoulos & Stephen A Cannistra & Helen Fountzilas & Aedin Culhane & Kamana Pillay & Bo Rueda & Daniel Cramer & Michael Seiden & Michael Birrer & George Coukos & Lin Zhang & John , 2011. "Integrated Analysis of Multiple Microarray Datasets Identifies a Reproducible Survival Predictor in Ovarian Cancer," PLOS ONE, Public Library of Science, vol. 6(3), pages 1-12, March.
  • Handle: RePEc:plo:pone00:0018202
    DOI: 10.1371/journal.pone.0018202
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