title: Determination of the differential expression of mitochondrial long non-coding RNAs as a noninvasive diagnosis of bladder cancer.
abstract: BACKGROUND
  Bladder cancer is a significant cause of morbidity and mortality with a high recurrence rate. Early detection of bladder cancer is essential in order to remove the tumor, to preserve the organ and to avoid metastasis. The aim of this study was to analyze the differential expression of mitochondrial non-coding RNAs (sense and antisense) in cells isolated from voided urine of patients with bladder cancer as a noninvasive diagnostic assay.
  
  
  METHODS
  The differential expression of the sense (SncmtRNA) and the antisense (ASncmtRNAs) transcripts in cells isolated from voided urine was determined by fluorescent in situ hybridization. The test uses a multiprobe mixture labeled with different fluorophores and takes about 1 hour to complete. We examined the expression of these transcripts in cells isolated from urine of 24 patients with bladder cancer and from 15 healthy donors.
  
  
  RESULTS
  This study indicates that the SncmtRNA and the ASncmtRNAs are stable in cells present in urine. The test reveals that the expression pattern of the mitochondrial transcripts can discriminate between normal and tumor cells. The analysis of 24 urine samples from patients with bladder cancer revealed expression of the SncmtRNA and down-regulation of the ASncmtRNAs. Exfoliated cells recovered from the urine of healthy donors do not express these mitochondrial transcripts. This is the first report showing that the differential expression of these mitochondrial transcripts can detect tumor cells in the urine of patients with low and high grade bladder cancer.
  
  
  CONCLUSIONS
  This pilot study indicates that fluorescent in situ hybridization of cells from urine of patients with different grades of bladder cancer confirmed the tumor origin of these cells. Samples from the 24 patients with bladder cancer contain cells that express the SncmtRNA and down-regulate the ASncmtRNAs. In contrast, the hybridization of the few exfoliated cells recovered from healthy donors revealed no expression of these mitochondrial transcripts. This assay can be explored as a non-invasive diagnostic tool for bladder cancer.
authors.affiliation: Andes Biotechnologies S.A. and Fundación Ciencia para la Vida, 7780272 Santiago, Chile.
authors.forename: Alexis
authors.initials: A
authors.lastname: Rivas
authors.forename: Verónica
authors.initials: V
authors.lastname: Burzio
authors.forename: Eduardo
authors.initials: E
authors.lastname: Landerer
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Borgna
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gatica
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Ávila
authors.forename: Constanza
authors.initials: C
authors.lastname: López
authors.forename: Claudio
authors.initials: C
authors.lastname: Villota
authors.forename: Rodrigo
authors.initials: R
authors.lastname: de la Fuente
authors.forename: Javiera
authors.initials: J
authors.lastname: Echenique
authors.forename: Luis O
authors.initials: LO
authors.lastname: Burzio
authors.forename: Jaime
authors.initials: J
authors.lastname: Villegas
mesh_terms: D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D010865:Pilot Projects; D012313:RNA / Q000032:analysis*; D062085:RNA, Long Noncoding / Q000032:analysis*; D000077278:RNA, Mitochondrial; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics; D014556:Urine / Q000166:cytology
chemical_list: D062085:RNA, Long Noncoding; D000077278:RNA, Mitochondrial; D012313:RNA