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|Title:||Periprostatic fat tissue transcriptome reveals a signature diagnostic for high-risk prostate cancer.|
|Epworth Authors:||Mangiola, Stefano|
Clarkson, Michael J
Costello, Anthony J
Hovens, Christopher M
Corcoran, Niall M
|Other Authors:||Macintyre, Geoff|
Peters, Justin S
|Keywords:||Epworth HealthCare, Victoria, Australia|
Altered Adipose Tissue Homeostasis
Periprostatic Adipose Tissue
|Citation:||Endocr Relat Cancer. 2018 May;25(5):pp.569-581.|
|Abstract:||Evidence suggests that altered adipose tissue homeostasis may be an important contributor to the development and/or progression of prostate cancer. In this study, we investigated the adipose transcriptional profiles of low- and high-risk disease to determine both prognostic potential and possible biological drivers of aggressive disease. RNA was extracted from periprostatic adipose tissue from patients categorised as having prostate cancer with either a low or high risk of progression based on tumour characteristics at prostatectomy and profiled by RNA sequencing. The expression of selected genes was then quantified by qRT-PCR in a cross-validation cohort. In the first phase, a total of 677 differentially transcribed genes were identified, from which a subset of 14 genes was shortlisted. In the second phase, a 3 gene (IGHA1, OLFM4, RERGL) signature was refined and evaluated using recursive feature selection and cross-validation, obtaining a promising discriminatory utility (area under curve 0.72) at predicting the presence of high-risk disease. Genes implicated in immune and/or inflammatory responses predominated. Periprostatic adipose tissue from patients with high-risk prostate cancer has a distinct transcriptional signature that may be useful for detecting its occult presence. Differential expression appears to be driven by a local immune/inflammatory reaction to more advanced tumours, than any specific adipose tissue-specific tumour-promoting mechanism. This signature is transferable into a clinically usable PCR-based assay, which in a cross-validation cohort shows diagnostic potential.|
|Journal Title:||Endocrine-Related Cancer|
|Affiliated Organisations:||Australian Prostate Cancer Research Centre Epworth, Richmond, Victoria, Australia|
Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia
Division of Bioinformatics, Walter and Eliza Hall Institute, Parkville, Victoria, Australia
Centre for Neural Engineering, Department of Computing and Information Systems, The University of Melbourne, Parkville, Victoria, Australia
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Diagnostic Genomics, NICTA, Victoria Research Laboratory, The University of Melbourne, Parkville, Victoria, Australia.
Department of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Department of Urology, Frankston Hospital, Frankston, Victoria, Australia.
|Appears in Collections:||Cancer Services|
Epworth Prostate Centre
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