A novel stratification framework for predicting outcome in patients with prostate cancer
Menée à partir de données génomiques portant sur 1 785 échantillons de cancer de la prostate, cette étude met en évidence l'intérêt d'une nouvelle approche, basée sur un algorithme permettant de détecter au niveau de chaque échantillon tumoral des signatures associées au risque d'échec biochimique ou de métastases, pour prédire les résultats oncologiques
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), , 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.
British Journal of Cancer , article en libre accès, 2020