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Genetic landscape of prostate cancer conspicuity on multiparametric MRI: a protocol for a systematic review and bioinformatic analysis.

ABSTRACT: INTRODUCTION:The introduction of multiparametric MRI (mpMRI) has enabled enhanced risk stratification for men at risk of prostate cancer, through accurate prebiopsy identification of clinically significant disease. However, approximately 10%-20% of significant prostate cancer may be missed on mpMRI. It appears that the genomic basis of lesion visibility or invisibility on mpMRI may have key implications for prognosis and treatment. Here, we describe a protocol for the first systematic review and novel bioinformatic analysis of the genomic basis of prostate cancer conspicuity on mpMRI. METHODS AND ANALYSIS:A systematic search of MEDLINE, PubMed, EMBASE and Cochrane databases will be conducted. Screening, data extraction, statistical analysis and reporting will be performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included papers will be full text articles, written between January 1980 and December 2019, comparing molecular characteristics of mpMRI-visible lesions and mpMRI-invisible lesions at the DNA, DNA-methylation, RNA or protein level. Study bias and quality will be assessed using a modified Newcastle-Ottawa score. Additionally, we will conduct a novel bioinformatic analysis of supplementary material and publicly available data, to combine transcriptomic data and reveal common pathways highlighted across studies. To ensure methodological rigour, this protocol is written in accordance with the PRISMA Protocol 2015 checklist. ETHICS AND DISSEMINATION:Ethical approval will not be required, as this is an academic review of published literature. Findings will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences. PROSPERO REGISTRATION NUMBER:CRD42019147423.

SUBMITTER: Norris JM

PROVIDER: S-EPMC7045175 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Genetic landscape of prostate cancer conspicuity on multiparametric MRI: a protocol for a systematic review and bioinformatic analysis.

Norris Joseph M JM Simpson Benjamin S BS Parry Marina A MA Allen Clare C Ball Rhys R Freeman Alex A Kelly Daniel D Kirkham Alex A Kasivisvanathan Veeru V Whitaker Hayley C HC Emberton Mark M

BMJ open 20200127 1

<h4>Introduction</h4>The introduction of multiparametric MRI (mpMRI) has enabled enhanced risk stratification for men at risk of prostate cancer, through accurate prebiopsy identification of clinically significant disease. However, approximately 10%-20% of significant prostate cancer may be missed on mpMRI. It appears that the genomic basis of lesion visibility or invisibility on mpMRI may have key implications for prognosis and treatment. Here, we describe a protocol for the first systematic re ...[more]

PMID: 31992607

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Project description:ContextMultiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain.ObjectiveTo systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study.Evidence acquisitionWe performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment.Evidence synthesisWe retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue (PTEN) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours.ConclusionsProstate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets.Patient summaryProstate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility.

Project description:IntroductionMultiparametric MRI (mpMRI) has improved risk stratification for men with suspected prostate cancer. Indeed, mpMRI-visible tumours tend to be larger and of higher pathological grade than mpMRI-invisible tumours; however, concern remains around significant cancer that is undetected by mpMRI. There has been considerable recent interest to investigate whether tumour conspicuity on mpMRI is associated with additional histopathological features (including cellular density, microvessel density and unusual prostate cancer subtypes), which may have important clinical implications in both diagnosis and prognosis. Furthermore, analysis of these features may help reveal the radiobiology that underpins the actual mechanisms of mpMRI visibility (and invisibility) of prostate tumours. Here, we describe a protocol for a systematic review of the histopathological basis of prostate cancer conspicuity on mpMRI.Methods and analysisA systematic search of the MEDLINE, PubMed, Embase and Cochrane databases will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be used to guide screening, thematic reporting and conclusions drawn from all eligible studies. Included papers will be full-text, English-language articles, comparing the histopathological characteristics of mpMRI-visible lesions and mpMRI-invisible tumours. All studies published between January 1950 and January 2020 will be eligible for inclusion. Studies using confirmatory immunohistochemistry for the identification of immune subsets or structural components will be included. Study bias and quality will be assessed using a modified Newcastle-Ottawa scale. To ensure methodological rigour, this protocol is written in accordance with the PRISMA Protocol 2015 checklist. If appropriate, a meta-analysis will be conducted comparing histopathological feature frequency between mpMRI-visible and mpMRI-invisible disease.Ethics and disseminationNo ethical approval will be required as this is an academic review of published literature. Findings will be disseminated through publications in peer-reviewed journals and presentations at national and international conferences.Prospero registration numberCRD42020176049.

Dataset Information

Genetic landscape of prostate cancer conspicuity on multiparametric MRI: a protocol for a systematic review and bioinformatic analysis.

Publications

Genetic landscape of prostate cancer conspicuity on multiparametric MRI: a protocol for a systematic review and bioinformatic analysis.

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