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Title: Reduction in expression of the benign AR transcriptome is a hallmark of localised prostate cancer progression.
Epworth Authors: Stuchbery, Ryan
Costello, Anthony
Hovens, Christopher
Corcoran, Niall
Harewood, Laurence
Other Authors: Cmero, Marek
Macintyre, Geoff
Peters, Justin
Keywords: Prostate Cancer
Prostate Neoplasms
PSA Screening
Androgen Receptor
AR Transcriptome
Androgen Signalling
Signalling Pathway Changes
Kaplan-Meier Curves
edgeR Bioconductor Package
Cox Regression
Student's T-Test
Australian Prostate Cancer Research Centre Epworth
Issue Date: Apr-2016
Publisher: Impact Journals
Citation: Oncotarget. 2016 Apr 22
Abstract: BACKGROUND: Despite the importance of androgen receptor (AR) signalling to prostate cancer development, little is known about how this signalling pathway changes with increasing grade and stage of the disease. OBJECTIVE: To explore changes in the normal AR transcriptome in localised prostate cancer, and its relation to adverse pathological features and disease recurrence. DESIGN: Publically accessible human prostate cancer expression arrays as well as RNA sequencing data from the prostate TCGA. Tumour associated PSA and PSAD were calculated for a large cohort of men (n=1108) undergoing prostatectomy. Outcome Measurements and Statistical Analysis: We performed a meta-analysis of the expression of an androgen-regulated gene set across datasets using Oncomine. Differential expression of selected genes in the prostate TCGA database was probed using the edgeR Bioconductor package. Changes in tumour PSA density with stage and grade were assessed by Student's t-test, and its association with biochemical recurrence explored by Kaplan-Meier curves and Cox regression. RESULTS: Meta-analysis revealed a systematic decline in the expression of a previously identified benign prostate androgen-regulated gene set with increasing tumour grade, reaching significance in nine of 25 genes tested despite increasing AR expression. These results were confirmed in a large independent dataset from the TCGA. At the protein level, when serum PSA was corrected for tumour volume, significantly lower levels were observed with increasing tumour grade and stage, and predicted disease recurrence. CONCLUSIONS: Lower PSA secretion-per-tumour-volume is associated with increasing grade and stage of prostate cancer, has prognostic relevance, and reflects a systematic perturbation of androgen signalling
Description: [epub ahead of print]
DOI: 10.18632/oncotarget.8915
PubMed URL:
ISSN: 1949-2553
Journal Title: Oncotarget
Type: Journal Article
Affiliated Organisations: Department of Urology, Royal Melbourne Hospital and University of Melbourne, Parkville, VIC, Australia
NICTA Victoria Research Laboratory, University of Melbourne, Parkville, VIC, Australia
Department of Surgery, Royal Melbourne Hospital and University of Melbourne, Parkville, VIC, Australia
Type of Clinical Study or Trial: Meta-Analysis
Appears in Collections:Cancer Services
UroRenal, Vascular
Epworth Prostate Centre

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