title: Serum miRNA biomarkers serve as a fingerprint for proliferative diabetic retinopathy.
abstract: BACKGROUND
  Diabetic retinopathy (DR) is a retinopathy resulting from diabetes mellitus (DM) which was classified into non-proliferative DR (NPDR) and proliferative DR (PDR). Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs) that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR.
  
  
  METHODS
  In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA). The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR) arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR.
  
  
  RESULTS
  Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC) curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%.
  
  
  CONCLUSIONS
  These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Shao
authors.initials: S
authors.lastname: Qing
authors.forename: Songtao
authors.initials: S
authors.lastname: Yuan
authors.forename: Chen
authors.initials: C
authors.lastname: Yun
authors.forename: Hang
authors.initials: H
authors.lastname: Hui
authors.forename: Pingan
authors.initials: P
authors.lastname: Mao
authors.forename: Fan
authors.initials: F
authors.lastname: Wen
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Ding
authors.forename: Qinghuai
authors.initials: Q
authors.lastname: Liu
mesh_terms: D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D003930:Diabetic Retinopathy / Q000097:blood* / Q000175:diagnosis*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D035683:MicroRNAs