A Novel Stratification Framework for Predicting Outcome in Patients with Prostate Cancer

Luca, Bogdan, Moulton, Vincent, Ellis, Christopher, Edwards, Dylan, Campbell, Colin, Cooper, Rosalin, Clark, Jeremy, Brewer, Daniel and Cooper, Colin (2020) A Novel Stratification Framework for Predicting Outcome in Patients with Prostate Cancer. British Journal of Cancer, 122 (10). 1467–1476. ISSN 0007-0920

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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.

Item Type: Article
Uncontrolled Keywords: breast,erg,gene-expression,genomic classifier,heterogeneity,high-risk,identification,integration,radical prostatectomy,validation
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Computing Sciences
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 12 Feb 2020 05:38
Last Modified: 14 Jul 2020 23:45
URI: https://ueaeprints.uea.ac.uk/id/eprint/74155
DOI: 10.1038/s41416-020-0799-5

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