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Serum microRNA analysis: A minimally invasive assay correlated with upgrading in patients with low-risk prostate cancer
Kari Bailey, MD, Christopher Lebeis, MD, Drew Palmer, MD, Shiv Patel, MD, Travis Sullivan, MS, David Canes, MD, Alireza Moinzadeh, MD, John A. Libertino, MD, Kimberly M. Rieger-Christ, PhD.
Lahey Hospital and Medical Center, Burlington, MA, USA.
Background
Pathologic upgrading from biopsy to prostatectomy occurs in approximately 30% of prostate cancer cases. PSA, a nonspecific protein, has previously been the primary serum marker for prostate cancer. Biomarkers that more accurately assess risk of aggressive prostate cancer at the time of screening are critical for the future management of this disease. The aim of this study was to identify a panel of microRNA (miRNA) from serum that could differentiate patients with low-risk (Gleason 6) prostate cancer on TRUS biopsy specimens who were either the same grade or upgraded at the time of prostatectomy.
Methods
Total RNA was isolated from serum of patients who had Gleason Sum (GS) 6 prostate cancer at the time of TRUS guided prostate biopsy. These patients were divided into groups with GS 6 that remained GS 6 (same grade) at prostatectomy and those who were upgraded to ≥GS7 (upgrade) at the time of prostatectomy. For the discovery phase, sample pools from each group were profiled via miRNA PCR array (Exiqon). Validation of miRNA expression levels was performed on 30 same and 30 upgrade samples by qRT-PCR.
Results
Array analysis of 751 miRNA identified 35 miRNA with ≥2-fold differential expression between patients who had Gleason upgrading between biopsies and prostatectomy compared to patients who were same grade. Of these, 21 miRNA were down-regulated and 14 were up-regulated in the upgraded group. Additionally, 3 miRNA were expressed in the upgrade group which were not detected in the same grade group. Several miRNA were further validated by qRT-PCR on individual samples which confirmed differential expression between the two study groups.
Conclusions
Serum samples demonstrated different miRNA expression levels between samples that were same grade or upgraded from Gleason 6 at prostatectomy. This minimally invasive assay could provide an adjunct to PSA and prostate biopsies to better counsel patients on management of low-risk prostate cancer and monitor patients on active surveillance.
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