Multiparametric Magnetic Resonance Imaging Features Identify Aggressive Prostate Cancer at the Phenotypic and Transcriptomic Level

Beksaç, Alp Tuna; Cumarasamy, Shivaram; Falagario, Ugo Giovanni; Xu, Paige; Takhar, Mandeep; Alshalalfa, Mohamed; Gupta, Akriti; Prasad, Sonya; Martini, Alberto; Thulasidass, Hari; Rai, Richa; Berger, Mark S.; Hectors, Stefanie; Jordan, Jennifer; Davicioni, Elai; Nair, Sujit S.; Haines, Kenneth; Lewis, Sara; Rastinehad, Ardeshir R.; Yadav, Kamlesh K; Jayaratna, Isuru; Taouli, Bachir; Tewari, Ashutosh

doi:10.1016/j.juro.2018.06.041

Cited by 23 publications

(14 citation statements)

References 25 publications

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“…Decipher, a genomic classifier (GC), is a 22-gene prognostic signature associated with early metastasis of prostate cancer [16] . Overall, mpMRI-visible tumours appear to have increased Decipher scores compared with mpMRI-invisible tumours, in both biopsy cohorts and radical prostatectomy cohorts [17] , [18] , [19] , [20] . In contrast, two recent studies found no major association of a GC-based gene signature and tumour conspicuity on mpMRI; however, this may be attributed to a small sample size ( n = 6) [21] and a low- to intermediate-risk cohort, mirroring similar results to studies using Oncotype DX in this patient population [13] , [15] , [22] .…”

Section: Evidence Synthesismentioning

confidence: 94%

“…Furthermore, Dulaney and colleagues [27] reported that tumours with a PI-RADS score of 5 had significantly more deregulation of pathways involved in apoptosis and cell cycle (in particular, TGFβ, STAT, and RAS pathways) compared with mpMRI-invisible tumours; however, this was unadjusted for multiple testing and this study scored relatively low using the modified Newcastle-Ottawa scale (3/8), indicating a potential a risk of bias. Finally, Beksac et al [17] reported that pathways associated with CCP (PI3K-AKT-mTOR and E2F) and castration resistance (WNT-b) were found to be more active in mpMRI-visible cancer (PI-RADSv2 score of 5) than in mpMRI-invisible cancer.…”

Section: Evidence Synthesismentioning

confidence: 99%

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Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

Norris

Simpson

Parry

et al. 2020

European Urology Open Science

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Context Multiparametric 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. Objective To 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 acquisition We 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 synthesis We 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. Conclusions Prostate 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 summary Prostate 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.

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Section: Evidence Synthesismentioning

confidence: 94%

Section: Evidence Synthesismentioning

confidence: 99%

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

Norris

Simpson

Parry

et al. 2020

European Urology Open Science

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“…Conversely, mpMRI naïve RCs offer the unique opportunity to potentially tailor further testing, such as mpMRI and PBx itself, on an individual basis. Indeed, it has been pointed out that RCs and biomarkers may help in selecting patients who could benefit from mpMRI and PBx and patients with a very low risk of csPCa in whom the positive predictive value of mpMRI is low and mpMRI and PBx should be avoided (29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Does Multiparametric Magnetic Resonance of Prostate Outperform Risk Calculators in Predicting Prostate Cancer in Biopsy Naïve Patients?

et al. 2021

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BackgroundEuropean Association of Urology (EAU) guidelines recommend using risk-calculators (RCs), imaging or additional biomarkers in asymptomatic men at risk of prostate cancer (PCa).ObjectivesTo compare the performance of mpMRI, a RC we recently developed and two commonly used RC not including mpMRI in predicting the risk of PCa, as well as the added value of mpMRI to each RC.Design, Setting, and ParticipantsSingle-center retrospective study evaluating 221 biopsy-naïve patients who underwent prebiopsy mpMRI.Outcome Measurements and Statistical AnalysisPatients’ probabilities of any PCa and clinically significant PCa (csPC, defined as Gleason-Score ≥3 + 4) were computed according to mpMRI, European Randomized Study of Screening for Prostate Cancer RC (ERSPC-RC), the Prostate Biopsy Collaborative Group RC (PBCG-RC) and the Foggia Prostate Cancer RC (FPC-RC). Logistic regression, AUC, and Decision curve analysis (DCA) were used to assess the accuracy of tested models.Results and LimitationThe FPC-RC outperformed mpMRI in diagnosing both any PCa (AUC 0.76 vs 0.69) and csPCa (AUC 0.80 vs 0.75). Conversely mpMRI showed a higher accuracy in predicting any PCa compared to the PBCG-RC and the ERSPC-RC but similar performances in predicting csPCa. At multivariable analysis predicting csPCa and any PCa, the addition of mpMRI findings improved the accuracy of each calculator. DCA showed that the FPC-RC provided a greater net benefit than mpMRI and the other RCs. The addition of mpMRI findings improved the net benefit provided by each calculator.ConclusionsmpMRI was outperformed by the novel FPC-RC and showed similar performances compared to the PBCG and ERSPC RCs in predicting csPCa. The addition of mpMRI findings improved the diagnostic accuracy of each of these calculators

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“…Perhaps the most relevant molecular characteristic that links to radiobiological mechanisms of tumor conspicuity is that mpMRI‐visible tumors appear to differentially express genes involved in cell growth and proliferation, when compared to mpMRI‐invisible tumors (Figure 1). Beksac and colleagues reported that pathways associated with cell cycle progression, specifically PI3K‐AKT‐mTOR, E2F, MYC target genes, and castration resistance genes ( WNT‐b ) tended to have the highest enrichment in the most visible tumors 49 . Furthermore, Li and colleagues undertook an impressive multiphase project, showing that mpMRI‐visible tumors have increased expression of genes involved in mitotic cell cycle, protein folding, cell cycle, mitotic cell cycle process, and cell division.…”

Section: Supportive Evidencementioning

confidence: 99%

“…Beksac and colleagues reported that pathways associated with cell cycle progression, specifically PI3K-AKT-mTOR, E2F, MYC target genes, and castration resistance genes (WNT-b) tended to have the highest enrichment in the most visible tumors. 49 Furthermore, Li and colleagues undertook an impressive multiphase project, showing that mpMRI-visible tumors have increased expression of genes involved in mitotic cell cycle, protein folding, cell cycle, mitotic cell cycle process, and cell division. These included genes that encode proteins, such as CENPF and GDF15.…”

Section: Cell Growth and Proliferationmentioning

confidence: 99%

Conspicuity of prostate cancer on multiparametric magnetic resonance imaging: A cross‐disciplinary translational hypothesis

et al. 2020

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Multiparametric Magnetic Resonance Imaging Features Identify Aggressive Prostate Cancer at the Phenotypic and Transcriptomic Level

Cited by 23 publications

References 25 publications

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis

Does Multiparametric Magnetic Resonance of Prostate Outperform Risk Calculators in Predicting Prostate Cancer in Biopsy Naïve Patients?

Conspicuity of prostate cancer on multiparametric magnetic resonance imaging: A cross‐disciplinary translational hypothesis

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