title: Urinary MicroRNAs of Prostate Cancer: Virus-Encoded hsv1-miRH18 and hsv2-miR-H9-5p Could Be Valuable Diagnostic Markers.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH.
  
  
  METHODS
  In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study. A urine-based miRNA microarray analysis suggested the presence of differentially expressed urinary miRNAs in patients with PCa, and these were further validated in three independent PCa cohorts, using a quantitative reverse transcriptionpolymerase chain reaction analysis.
  
  
  RESULTS
  The expression levels of hsa-miR-615-3p, hsv1-miR-H18, hsv2-miR-H9-5p, and hsa-miR-4316 were significantly higher in urine samples of patients with PCa than in those of BPH controls. In particular, herpes simplex virus (hsv)-derived hsv1-miR-H18 and hsv2-miR-H9-5p showed better diagnostic performance than did the serum prostate-specific antigen (PSA) test for patients in the PSA gray zone. Furthermore, a combination of urinary hsv2-miR-H9-5p with serum PSA showed high sensitivity and specificity, providing a potential clinical benefit by reducing unnecessary biopsies.
  
  
  CONCLUSIONS
  Our findings showed that hsv-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are significantly associated with PCa and can facilitate early diagnosis of PCa for patients within the serum PSA gray zone.
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Seok Joong
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Pildu
authors.initials: P
authors.lastname: Jeong
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Ho Won
authors.initials: HW
authors.lastname: Kang
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Ye-Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Eun-Ah
authors.initials: EA
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Chunri
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Korea.
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Choi
authors.affiliation: Bio Medical Laboratories (BML), Daejeon, Korea.
authors.forename: Dongho
authors.initials: D
authors.lastname: Kim
authors.affiliation: NAR Center Inc., Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Medical Genomics Research Center, Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Department of Functional Genomics, University of Science and Technology, Daejeon, Korea.
authors.forename: Seon-Kyu
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Medical Genomics Research Center, Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Department of Functional Genomics, University of Science and Technology, Daejeon, Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Biomedical Research Institute, Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
authors.forename: Sang Tae
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Won Tae
authors.initials: WT
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Ok-Jun
authors.initials: OJ
authors.lastname: Lee
authors.affiliation: National Research Laboratory of Vascular Biology and Stem Cells, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Gou-Young
authors.initials: GY
authors.lastname: Koh
authors.affiliation: School of Food Science and Technology, Chung-Ang University, Anseong, Korea.
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.affiliation: The Section of Urologic Oncology and Dean and Betty Gallo Prostate Cancer Center, The Cancer Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Isaac Yi
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, MA, USA ; Division of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA ; Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Jayoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Korea.
authors.forename: Yung-Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
keywords: Herpes Simplex; MicroRNA; Prostate Cancer; Urine