title: MicroRNA molecular profiling from matched tumor and bio-fluids in bladder cancer.
abstract: BACKGROUND
  MicroRNAs have been identified as potential cancer biomarkers due to their presence and stability in many body fluids including urine and plasma, but the relationship of the pattern of expression of these messengers across various biological media has not been addressed and could provide important information in order to translate these biomarkers for epidemiologic or clinical use.
  
  
  METHODS
  We analyzed microRNA of matched FFPE-tumor tissue, plasma, urine exosomes (n = 16) and WBCs (n = 11) from patients with bladder cancer, using Nanostring miRNA assays and droplet digital PCR for validation. Pearson correlations were used to compare expression between media.
  
  
  RESULTS
  Numerous microRNAs were detected and overlapping from specific bio-specimen sources. MiR-4454 and miR-21 overexpression was found in three sources: tumor, WBCs and urine. Additionally, miR-15b-5p, miR-126-3p, miR-93-5p, and miR-150-5p were common to tumor/WBCs, while miR-720/3007a, miR-205, miR-200c-3p and miR-29b-3p common to tumor/urine. Significant associations were noted between the log-adjusted average miRNA counts in tumor vs. WBCs (r = 0.418 p < 0.001), and tumor vs. urine (r = 0.38 p < 0.001). No association was seen tumor vs. plasma exosome miRs (r = 0.07 p = 0.06).
  
  
  CONCLUSIONS
  MicroRNA profiling from matched samples in patients shows a significant number of microRNAs up regulated in bladder tumors are identifiable in urine exosomes and WBCs of the same patient, but not in blood plasma. This study demonstrated varying relationships between miRNA detected in biological media from the same patient, and serves to inform the potential of urine-based microRNAs as biomarkers for bladder cancer and potentially other malignancies.
authors.affiliation: Departments of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. David.Armstrong@Dartmouth.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Armstrong
authors.affiliation: Departments of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. Benjamin.B.Green@Dartmouth.edu.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Green
authors.affiliation: Department of Surgery (Urology), Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. John.D.Seigne@Dartmouth.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Seigne
authors.affiliation: Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. Alan.R.Schned@Dartmouth.edu.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Schned
authors.affiliation: Departments of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. Carmen.J.Marsit@dartmouth.edu.|Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. Carmen.J.Marsit@dartmouth.edu.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D055354:Exosomes / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C527111:MIRN126 microRNA, human; D035683:MicroRNAs