A novel stratification framework for predicting outcome in patients with prostate cancer

Bogdan Luca, Vincent Moulton, Christopher Ellis, Dylan Edwards, Colin Campbell, Rosalin Cooper, Jeremy Clark, Daniel Brewer, Colin Cooper

Research output: Contribution to journalArticle

4 Citations (Scopus)
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Abstract

Background: Unsupervised learning methods, such as Hierarchical Cluster Analysis, are commonly used for the analysis of genomic platform data. Unfortunately, such approaches ignore the well-documented heterogeneous composition of prostate cancer samples. Our aim is to use more sophisticated analytical approaches to deconvolute the structure of prostate cancer transcriptome data, providing novel clinically actionable information for this disease. Methods: We apply an unsupervised model called Latent Process Decomposition (LPD), which can handle heterogeneity within individual cancer samples, to genome-wide expression data from eight prostate cancer clinical series, including 1,785 malignant samples with the clinical endpoints of PSA failure and metastasis. Results: We show that PSA failure is correlated with the level of an expression signature called DESNT (HR = 1.52, 95% CI = [1.36, 1.7], P = 9.0 × 10 −14, Cox model), and that patients with a majority DESNT signature have an increased metastatic risk (X 2 test, P = 0.0017, and P = 0.0019). In addition, we develop a stratification framework that incorporates DESNT and identifies three novel molecular subtypes of prostate cancer. Conclusions: These results highlight the importance of using more complex approaches for the analysis of genomic data, may assist drug targeting, and have allowed the construction of a nomogram combining DESNT with other clinical factors for use in clinical management.

Original languageEnglish
Pages (from-to)1467–1476
Number of pages10
JournalBritish Journal of Cancer
Volume122
Issue number10
Early online date20 Mar 2020
DOIs
Publication statusPublished - 12 May 2020

Keywords

  • BREAST
  • ERG
  • GENE-EXPRESSION
  • GENOMIC CLASSIFIER
  • HETEROGENEITY
  • HIGH-RISK
  • IDENTIFICATION
  • INTEGRATION
  • RADICAL PROSTATECTOMY
  • VALIDATION

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