Int Neurourol J.  2015 Jun;19(2):74-84. 10.5213/inj.2015.19.2.74.

Urinary MicroRNAs of Prostate Cancer: Virus-Encoded hsv1-miRH18 and hsv2-miR-H9-5p Could Be Valuable Diagnostic Markers

Affiliations
  • 1Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea. wjkim@chungbuk.ac.kr
  • 2Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Korea.
  • 3Bio Medical Laboratories (BML), Daejeon, Korea.
  • 4NAR Center Inc., Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea.
  • 5Medical Genomics Research Center, Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Department of Functional Genomics, University of Science and Technology, Daejeon, Korea.
  • 6Biomedical Research Institute, Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  • 7Department of Pathology, Chungbuk National University College of Medicine, Cheongju, Korea.
  • 8National Research Laboratory of Vascular Biology and Stem Cells, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
  • 9School of Food Science and Technology, Chung-Ang University, Anseong, Korea.
  • 10The 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.
  • 11Department of Surgery, Harvard Medical School, Boston, MA, USA.
  • 12Division of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • 13Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
  • 14Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Korea.

Abstract

PURPOSE
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.

Keyword

Prostate Cancer; Urine; Herpes Simplex; MicroRNA

MeSH Terms

Biomarkers
Biopsy
Cohort Studies
Diagnosis
Early Diagnosis
Herpes Simplex
Humans
Microarray Analysis
MicroRNAs*
Passive Cutaneous Anaphylaxis
Prostate
Prostate-Specific Antigen
Prostatic Hyperplasia
Prostatic Neoplasms*
Sensitivity and Specificity
Simplexvirus
Urologic Diseases
MicroRNAs
Prostate-Specific Antigen
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