title: Downregulation of urinary cell-free microRNA-214 as a diagnostic and prognostic biomarker in bladder cancer.
abstract: OBJECTIVE
  We aimed to investigate potential of urinary cell-free microRNA-214 (miR-214) as a noninvasive biomarker for bladder cancer in this report.
  
  
  METHODS
  We screened miR-214 expression in medium from 2 bladder cancer cell lines to determine whether it is secretory. Then we validated expression of cell-free miR-214 in urine samples from an independent set of 192 preoperative bladder cancer patients, 80 matching postoperative patients and 169 healthy controls.
  
  
  RESULTS
  miR-214 was secreted from bladder cancer cell lines. Cell-free miR-214 levels were significantly attenuated in preoperative urine from bladder cancer patients, whereas its expression significantly increased in matched postoperative urine. Underexpressed extracellular miR-214 in urine was significantly associated with higher tumor stage, higher lymph node status, higher grade, age and history of non-muscle-invasive bladder cancer (NMIBC). Urinary cell-free miR-214 could forcefully differentiate bladder cancer (area under the curve; AUC = 0.838; 95% CI = 0.796-0.875) patients from healthy controls. Additionally, miR-214 in urine supernatant could serve as an independent prognostic predicator of recurrence-free survival (RFS) and overall survival (OS) for patients with muscle-invasive bladder cancer (MIBC).
  
  
  CONCLUSIONS
  Urinary cell-free miR-214 is a hopeful biomarker for tumor stratification, early diagnosis and prognostic assessment of bladder cancer.
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.|Department of Clinical Laboratory, Linyi People's Hospital, Linyi, Shandong Province, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Lutao
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Geriatrics, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Chuanxin
authors.initials: C
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000652:urine*; D045744:Cell Line, Tumor / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000652:urine*; D008875:Middle Aged; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; C547397:MIRN214 microRNA, human; D035683:MicroRNAs
keywords: bladder cancer; cell-free miR-214; circulating miRNAs; non-invasive diagnosis; prognostic factor