Integrative (epi) Genomic Analysis to Predict Response to Androgen-Deprivation Therapy in Prostate Cancer

Therapeutic resistance is a central problem in clinical oncology. We have developed a systematic genome-wide computational methodology to allow prioritization of patients with favorable and poor therapeutic response. Our method, which integrates DNA methylation and mRNA expression data, uncovered a panel of 5 differentially methylated sites, which explain expression changes in their site-harboring genes, and demonstrated their ability to predict primary resistance to androgen-deprivation therapy (ADT) in the TCGA prostate cancer patient cohort (hazard ratio = 4.37). Furthermore, this panel was able to accurately predict response to ADT across independent prostate cancer cohorts and demonstrated that it was not affected by Gleason, age, or therapy subtypes. We propose that this panel could be utilized to prioritize patients who would benefit from ADT and patients at risk of resistance that should be offered an alternative regimen. Such approach holds a long-term objective to build an adaptable accurate platform for precision therapeutics. Keywords: Therapeutic resistance, DNA methylation, mRNA expression, Epigenomics, Androgen-deprivation, Prostate cancer

Abstract licence: CC BY-NC

1. 4.

   Molecular sampling of prostate cancer: a dilemma for predicting disease progression · 2010

2. 19.

   pROC: an open-source package for R and S+ to analyze and compare ROC curves · 2011

3. 30.

   Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis · 2010

37 more references, whose wording the paper’s licence keeps private.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.