Periprostatic fat tissue transcriptome reveals a signature diagnostic for high-risk prostate cancer
| Autor: | Justin S. Peters, Michael J Clarkson, Stefano Mangiola, Niall M. Corcoran, Geoff Macintyre, Christopher M. Hovens, Anthony J. Costello, Ryan Stuchbery |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research Endocrinology Diabetes and Metabolism Adipose tissue Disease Transcriptome 03 medical and health sciences Prostate cancer 0302 clinical medicine Endocrinology Periprostatic Prostate Risk Factors Biopsy Medicine Humans Aged medicine.diagnostic_test business.industry Cancer Prostatic Neoplasms Middle Aged medicine.disease Prognosis 030104 developmental biology medicine.anatomical_structure Oncology Adipose Tissue 030220 oncology & carcinogenesis Cancer research business |
| Zdroj: | Endocrine-related cancer. 25(5) |
| ISSN: | 1479-6821 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|