Identification and Validation of a Five MicroRNA Signature Predictive of Prostate Cancer Recurrence and Metastasis: A Cohort Study.

MicroRNA (miRNA) have been shown to be important in regulating gene expression in prostate cancer. We used next generation miRNA sequencing to conduct a whole miRNome analysis to identify miRNAs associated with prostate cancer metastasis.

We conducted discovery and validation analyses of miRNAs among a total of 546 men who underwent surgery for prostate cancer using the development of metastasis as an endpoint. Genome wide analysis was conducted among the discovery group (n=31) to identify new miRNAs associated with prostate cancer metastasis. Selected miRNAs were then analyzed using qPCR on prostatectomy specimens from an independent cohort (n=515) to determine whether their expression could predict the development of metastasis after surgery. To examine the biology underlying these associations, we created prostate cancer cell lines which overexpressed miR-301a for in vitro and in vivo functional assays.

We identified 33 miRNAs associated with prostate cancer metastasis and selected a panel comprising miRs-301a, 652, 454, 223 and 139 which strongly predicted metastasis (AUC=95. 3%, 95%C. I. :84%-99%). Among the validation cohort, the 15-year metastasis-free survival was 77. 5% (95% C. I. :63. 9%-86. 4%) for patients with a high miRNA panel score and 98. 8% (95% C. I. :94. 9%-99. 7%, p

A panel of miRNAs is associated with prostate cancer metastasis. These could be used as potential new prognostic factors in the surgical management of prostate cancer.

Journal of Cancer. 2015 Sep 15*** epublish ***

Robert K Nam, Yutaka Amemiya, Tania Benatar, Christopher J D Wallis, Jessica Stojcic-Bendavid, Stephanie Bacopulos, Christopher Sherman, Linda Sugar, Magda Naeim, Wenyi Yang, Aiguo Zhang, Laurence H Klotz, Steven A Narod, Arun Seth

1. Division of Urology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 2. Department of Anatomic Pathology, Platform Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 2. Department of Anatomic Pathology, Platform Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 1. Division of Urology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 1. Division of Urology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 2. Department of Anatomic Pathology, Platform Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 3. Department of Laboratory Medicine and Pathobiology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 3. Department of Laboratory Medicine and Pathobiology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 3. Department of Laboratory Medicine and Pathobiology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 2. Department of Anatomic Pathology, Platform Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 2. Department of Anatomic Pathology, Platform Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 1. Division of Urology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada. , 4. Department of Public Health Sciences, University of Toronto, 790 Bay St. , Toronto, ON, M5G 1N8, Canada. , 2. Department of Anatomic Pathology, Platform Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave. , Toronto, ON, M4N3M5, Canada.

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