A novel stratification framework for predicting outcome in patients with prostate cancer.
Ontology highlight
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 (X2 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.
SUBMITTER: Luca BA
PROVIDER: S-EPMC7217762 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
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