Prediction of Grade Reclassification of Prostate Cancer Patients on Active Surveillance through the Combination of a Three-miRNA Signature and Selected Clinical Variables

Published on May 18, 2021in Cancers6.126
· DOI :10.3390/CANCERS13102433
Paolo Gandellini25
Estimated H-index: 25
Chiara Maura Ciniselli14
Estimated H-index: 14
+ 13 AuthorsNadia Zaffaroni66
Estimated H-index: 66
Active surveillance (AS) has evolved as a strategy alternative to radical treatments for very low risk and low-risk prostate cancer (PCa). However, current criteria for selecting AS patients are still suboptimal. Here, we performed an unprecedented analysis of the circulating miRNome to investigate whether specific miRNAs associated with disease reclassification can provide risk refinement to standard clinicopathological features for improving patient selection. The global miRNA expression profiles were assessed in plasma samples prospectively collected at baseline from 386 patients on AS included in three independent mono-institutional cohorts (training, testing and validation sets). A three-miRNA signature (miR-511-5p, miR-598-3p and miR-199a-5p) was found to predict reclassification in all patient cohorts (training set: AUC 0.74, 95% CI 0.60–0.87, testing set: AUC 0.65, 95% CI 0.51–0.80, validation set: AUC 0.68, 95% CI 0.56–0.80). Importantly, the addition of the three-miRNA signature improved the performance of the clinical model including clinicopathological variables only (AUC 0.70, 95% CI 0.61–0.78 vs. 0.76, 95% CI 0.68–0.84). Overall, we trained, tested and validated a three-miRNA signature which, combined with selected clinicopathological variables, may represent a promising biomarker to improve on currently available clinicopathological risk stratification tools for a better selection of truly indolent PCa patients suitable for AS.
#1Simpa S. Salami (UM: University of Michigan)H-Index: 12
#2Jeffrey J. Tosoian (UM: University of Michigan)H-Index: 1
Last. Ganesh S. Palapattu (UM: University of Michigan)H-Index: 43
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Abstract Background The potential for low-grade (grade group 1 [GG1]) prostate cancer (PCa) to progress to high-grade disease remains unclear. Objective To interrogate the molecular and biological features of low-grade PCa serially over time. Design, setting, and participants Nested longitudinal cohort study in an academic active surveillance (AS) program. Men were on AS for GG1 PCa from 2012 to 2017. Intervention Electronic tracking and resampling of PCa using magnetic resonance imaging/ultraso...
1 CitationsSource
#1James Liu (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 7
#2Hiten D. Patel (Loyola University Medical Center)H-Index: 23
Last. Alan W. Partin (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 125
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Early identification and management of prostate cancer completely changed with the discovery of prostate-specific antigen. However, improved detection has also led to overdiagnosis and consequently overtreatment of patients with low-risk disease. Strategies for the management of patients using active surveillance — the monitoring of clinically insignificant disease until intervention is warranted — were developed in response to this issue. The success of this approach is critically dependent on ...
#1Edward M. Schaeffer (NU: Northwestern University)H-Index: 59
#2Sandy Srinivas (Stanford University)H-Index: 50
Last. Deborah A. Freedman-Cass (National Comprehensive Cancer Network)H-Index: 27
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The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease. Recommendations for disease monitoring and treatment of recurrent disease are also included. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. This article summarize...
2 CitationsSource
#1Zeyad R. Schwen (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 9
#1Zeyad Schwen (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 14
Last. Christian P. Pavlovich (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 51
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OBJECTIVE To identify the value of combining the Prostate Health Index (PHI) and multiparametric magnetic resonance imaging (mpMRI), tools which have previously been shown to be independently predictive of prostate cancer (PCa) grade reclassification (GR; Gleason score >6), for the purpose of predicting GR at the next surveillance biopsy to reduce unnecessary prostate biopsies for men in PCa active surveillance (AS). PATIENTS AND METHODS Between 2014 and 2019, we retrospectively identified 253 c...
7 CitationsSource
: Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasm...
6 CitationsSource
#2Degu AbateH-Index: 17
Last. Christopher J L MurrayH-Index: 225
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Importance Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving ...
334 CitationsSource
#1Serena Di CosimoH-Index: 31
#2Valentina AppiertoH-Index: 16
Last. Maria Grazia DaidoneH-Index: 75
view all 16 authors...
Purpose: To investigate the potential of circulating-microRNAs (ct-miRNAs) as non-invasive biomarkers to predict the efficacy of single/dual HER2-targeted therapy in the NeoALTTO study. Experimental Design: Patients with plasma samples at baseline (T0) and/or after two weeks (T1) of treatment were randomized into training (n=183) and testing (n=246) sets. RT-PCR-based high-throughput miRNA-profiling was employed in the training set. After normalization, ct-miRNAs associated with pathologic Compl...
11 CitationsSource
#1Wang C (Jining Medical University)H-Index: 1
#2Fan HqH-Index: 1
Last. Zhang YwH-Index: 1
view all 3 authors...
OBJECTIVE: Previous studies have revealed that miR-511-5p was abnormally expressed in several cancers. In this study, we aimed to develop a study on the expression patterns, clinical value, and functional roles of miR-511-5p in colorectal cancer (CRC). PATIENTS AND METHODS: MiR-511-5p and GPR116 were analyzed in CRC cell lines and tumor specimens by Real-time PCR. The clinical correlations between miR-511-5p expression and the clinicopathologic factors and prognosis were analyzed. The potential ...
3 CitationsSource
#1Paolo GandelliniH-Index: 25
#2Nicola Casiraghi (University of Trento)H-Index: 7
Last. Nadia ZaffaroniH-Index: 66
view all 11 authors...
Abstract Background Genomic characterization of prostate cancer (PCa) biopsies may improve criteria for the selection of patients suitable for active surveillance (AS). Objective To identify somatic genomic aberrations associated with adverse outcome as AS protocol exclusion indicators. Design, setting and participants Whole-exome sequencing profiles were generated for Gleason score (GS) = 3 + 3 biopsies obtained from 54 PCa patients enrolled in two AS protocols. Patients were selected as repres...
1 CitationsSource
#1Fang Zhao (Lunenfeld-Tanenbaum Research Institute)H-Index: 7
#2Danny Vesprini (Sunnybrook Research Institute)H-Index: 33
Last. Bharati Bapat (U of T: University of Toronto)H-Index: 64
view all 8 authors...
Abstract Purpose Prostate cancer (CaP) patients with low-grade tumors are enrolled in active surveillance (AS) programs and monitored with digital rectal exams (DREs), prostate-specific antigen (PSA) tests, and periodic invasive biopsies. Patients are “reclassified” with higher-risk disease if they show signs of disease progression. However, AS patients who will reclassify cannot be easily identified upfront and suffer morbidities associated with biopsy. Biomarkers derived from noninvasively obt...
8 CitationsSource
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