title: Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer.
abstract: BACKGROUND
  Extracellular microRNAs (miRNAs) embedded in circulating exosomes may serves as prognostic biomarkers in cancer.
  
  
  OBJECTIVE
  To identify and evaluate plasma exosomal miRNAs for prognosis in castration-resistant prostate cancer (CRPC).
  
  
  METHODS
  RNA sequencing was performed to identify candidate exosomal miRNAs associated with overall survival in a screening cohort of 23 CRPC patients. Candidate miRNAs were further evaluated for prognosis using quantitative real-time polymerase chain reaction in a follow-up cohort of 100 CRPC patients.
  
  
  METHODS
  Cox regression and Kaplan-Meier survival analyses were used to evaluate survival association using candidate miRNAs along with clinical prognostic factors.
  
  
  CONCLUSIONS
  RNA sequencing in screening cohort generated approximately 6.80 million mappable reads per patient. Of those with normalized read counts ≥ 5, 43% were mapped to miRNAs for a total of 375 known and 57 novel miRNAs. Cox regression analysis identified an association of miR-1290, -1246, and -375 with overall survival (false discover rate < 0.05). Of those, higher levels of miR-1290 and -375 were significantly associated with poor overall survival (p < 0.004) in the follow-up cohort. Incorporation of miR-1290/-375 into putative clinical prognostic factors-based models in CRPC stage significantly improved predictive performance with a time-dependent area under the curve increase from 0.66 to 0.73 (p = 6.57 × 10(-6)).
  
  
  CONCLUSIONS
  Plasma exosomal miR-1290 and miR-375 are promising prognostic biomarkers for CRPC patients. Prospective validation is needed for further evaluation of these candidate miRNAs.
  
  
  RESULTS
  In this study, we evaluated whether small RNAs circulating in blood could be used to predict clinical outcomes in late-stage prostate cancer patients. We identified two blood-based small RNAs whose levels showed significant association with survival. Our results warrant further investigation because the noninvasive blood-based test has great potential in the management of late-stage prostate cancer.
authors.affiliation: Department of Pathology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA; Biotherapy Center, Third Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pathology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Tiezheng
authors.initials: T
authors.lastname: Yuan
authors.affiliation: Department of Endocrinology, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Liang
authors.affiliation: Department of Pathology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Meijun
authors.initials: M
authors.lastname: Du
authors.affiliation: Department of Pathology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Xia
authors.affiliation: Department of Pathology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Dittmar
authors.affiliation: Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Dian
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Urology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: William
authors.initials: W
authors.lastname: See
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Costello
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Quevedo
authors.affiliation: Department of Oncology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Winston
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Debashis
authors.initials: D
authors.lastname: Nandy
authors.affiliation: University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Graham H
authors.initials: GH
authors.lastname: Bevan
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sherri
authors.initials: S
authors.lastname: Longenbach
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Boardman
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, MN, USA. Electronic address: kohli.manish@mayo.edu.
authors.forename: Manish
authors.initials: M
authors.lastname: Kohli
authors.affiliation: Department of Pathology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: liwang@mcw.edu.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D055354:Exosomes; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000235:genetics*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C574604:MIRN1290 microRNA, human; C540933:MIRN375 microRNA, human; D035683:MicroRNAs
keywords: Biomarker; Exosome; Extracellular RNA; Prognosis; Prostate cancer; RNA sequencing; Survival; microRNA