title: Plasma microRNA profiles for bladder cancer detection.
abstract: BACKGROUND
  Bladder cancer (BC) is a burdensome disease with significant morbidity, mortality, and cost. The development of novel plasma-based biomarkers for BC diagnosis and surveillance could significantly improve clinical outcomes and decrease health expenditures. Plasma miRNAs are promising biomarkers that have yet to be rigorously investigated in BC.
  
  
  OBJECTIVE
  To determine the feasibility and efficacy of detecting BC with plasma miRNA signatures.
  
  
  METHODS
  Plasma miRNA was isolated from 20 patients with bladder cancer and 18 noncancerous controls. Samples were analyzed with a miRNA array containing duplicate probes for each miRNA in the Sanger database. Logistic regression modeling was used to optimize diagnostic miRNA signatures to distinguish between muscle invasive BC (MIBC), non-muscle-invasive BC (NMIBC) and noncancerous controls.
  
  
  RESULTS
  Seventy-nine differentially expressed plasma miRNAs (local false discovery rate [FDR] <0.5) in patients with or without BC were identified. Some diagnostically relevant miRNAs, such as miR-200b, were up-regulated in MIBC patients, whereas others, such as miR-92 and miR-33, were inversely correlated with advanced clinical stage, supporting the notion that miRNAs released in the circulation have a variety of cellular origins. Logistic regression modeling was able to predict diagnosis with 89% accuracy for detecting the presence or absence of BC, 92% accuracy for distinguishing invasive BC from other cases, 100% accuracy for distinguishing MIBC from controls, and 79% accuracy for three-way classification between MIBC, NIMBC, and controls.
  
  
  CONCLUSIONS
  This study provides preliminary data supporting the use of plasma miRNAs as a noninvasive means of BC detection. Future studies will be required to further specify the optimal plasma miRNA signature, and to apply these signatures to clinical scenarios, such as initial BC detection and BC surveillance.
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Liana
authors.initials: L
authors.lastname: Adam
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Wszolek
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Wang
authors.initials: W
authors.lastname: Jing
authors.forename: Lixia
authors.initials: L
authors.lastname: Diao
authors.forename: Alexander
authors.initials: A
authors.lastname: Zien
authors.forename: Jitao D
authors.initials: JD
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Jackson
authors.forename: Colin P N
authors.initials: CP
authors.lastname: Dinney
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D003937:Diagnosis, Differential; D005240:Feasibility Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D059467:Transcriptome; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs