Dataset Information

Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations.

ABSTRACT:

Introduction

In the last decade microRNAs (miRNAs) have been widely investigated in prostate cancer (PCa) and have shown to be promising biomarkers in diagnostic, prognostic and predictive settings. However, tumor heterogeneity may influence miRNA expression. The aims of this study were to assess the impact of tumor heterogeneity, as demonstrated by a panel of selected miRNAs in PCa, and to correlate miRNA expression with risk profile and patient outcome.

Material and methods

Prostatectomy specimens and matched, preoperative needle biopsies from a retrospective cohort of 49 patients, who underwent curatively intended surgery for localized PCa, were investigated with a panel of 6 miRNAs (miRNA-21, miRNA-34a, miRNA-125b, miRNA-126, miRNA-143, and miRNA-145) using tissue micro-array (TMA) and in situ hybridization (ISH). Inter- and intra-patient variation was assessed using intra-class correlation (ICC).

Results

Four miRNAs (miRNA-21, miRNA-34a, miRNA-125, and miRNA-126) were significantly upregulated in PCa compared to benign prostatic hyperplasia (BPH), and except for miRNA-21 these miRNAs documented a positive correlation between the expression level in PCa cores and their matched BPH cores, (r > 0.72). The ICC varied from 0.451 to 0.764, with miRNA-34a showing an intra-tumoral heterogeneity accounting for less than 50% of the total variation. Regarding clinicopathological outcomes, only miRNA-143 showed potential as a prognostic marker with a higher expression correlating with longer relapse-free survival (p = 0.016).

Conclusion

The present study documents significant upregulation of the expression of miRNA-21, miRNA-34a, miRNA-125, and miRNA-126 in PCa compared to BPH and suggests a possible prognostic value associated with the expression of miRNA-143. The results, however, document intra-tumoral heterogeneity in the expression of various miRNAs calling for caution when using these tumor tissue biomarkers in prognostic and predictive settings.

SUBMITTER: Zedan AH

PROVIDER: S-EPMC5476257 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations.

Zedan Ahmed Hussein AH Blavnsfeldt Søren Garm SG Hansen Torben Frøstrup TF Nielsen Boye Schnack BS Marcussen Niels N Pleckaitis Mindaugas M Osther Palle Jörn Sloth PJS Sørensen Flemming Brandt FB

PloS one 20170619 6

<h4>Introduction</h4>In the last decade microRNAs (miRNAs) have been widely investigated in prostate cancer (PCa) and have shown to be promising biomarkers in diagnostic, prognostic and predictive settings. However, tumor heterogeneity may influence miRNA expression. The aims of this study were to assess the impact of tumor heterogeneity, as demonstrated by a panel of selected miRNAs in PCa, and to correlate miRNA expression with risk profile and patient outcome.<h4>Material and methods</h4>Pros ...[more]

PMID: 28628624

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Project description:BackgroundNext-generation sequencing is revealing genomic heterogeneity in localized prostate cancer (CaP). Incomplete sampling of CaP multiclonality has limited the implications for molecular subtyping, stratification, and systemic treatment.ObjectiveTo determine the impact of genomic and transcriptomic diversity within and among intraprostatic CaP foci on CaP molecular taxonomy, predictors of progression, and actionable therapeutic targets.Design, setting, and participantsFour consecutive patients with clinically localized National Comprehensive Cancer Network intermediate- or high-risk CaP who did not receive neoadjuvant therapy underwent radical prostatectomy at Roswell Park Cancer Institute in June-July 2014. Presurgical information on CaP content and a customized tissue procurement procedure were used to isolate nonmicroscopic and noncontiguous CaP foci in radical prostatectomy specimens. Three cores were obtained from the index lesion and one core from smaller lesions. RNA and DNA were extracted simultaneously from 26 cores with ≥90% CaP content and analyzed using whole-exome sequencing, single-nucleotide polymorphism arrays, and RNA sequencing.Outcome measurements and statistical analysisSomatic mutations, copy number alternations, gene expression, gene fusions, and phylogeny were defined. The impact of genomic alterations on CaP molecular classification, gene sets measured in Oncotype DX, Prolaris, and Decipher assays, and androgen receptor activity among CaP cores was determined.Results and limitationsThere was considerable variability in genomic alterations among CaP cores, and between RNA- and DNA-based platforms. Heterogeneity was found in molecular grouping of individual CaP foci and the activity of gene sets underlying the assays for risk stratification and androgen receptor activity, and was validated in independent genomic data sets. Determination of the implications for clinical decision-making requires follow-up studies.ConclusionsGenomic make-up varies widely among CaP foci, so care should be taken when making treatment decisions based on a single biopsy or index lesions.Patient summaryWe examined the molecular composition of individual cancers in a patient's prostate. We found a lot of genetic diversity among these cancers, and concluded that information from a single cancer biopsy is not sufficient to guide treatment decisions.

Dataset Information

Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations.

Introduction

Material and methods

Results

Conclusion

Publications

Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations.

Similar Datasets

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