title: Clinical verification of a novel urinary microRNA panal: 133b, -342 and -30 as biomarkers for diabetic nephropathy identified by bioinformatics analysis.
abstract: BACKGROUND
  Because microvascular disease is one of the major drivers of diabetic complications, early detection of diabetic nephropathy (DN) by assessing the expression of exosomal microRNAs (miRNAs) in DN patients and healthy controls, may be of clinical value. The aim of this study wasto identify a novel miRNA panel of DN by combining bioinformatics analysis of miRNA databases and clinical verification to evaluate the significance of this panel as urine biomarkers for type 2 diabetic nephropathy (T2DN).
  
  
  METHODS
  Public miRNA databases e.g miro-Ontology and miRWalk were analyzed and a novel panel of 3 microRNAs was retrieved. Meanwhile, combinatorial target prediction algorithms were applied. Multiple case-matched normal were examined by quantative RT-PCR for differential expression in urine exosomes from 210 participants, and the three identified miRNAs were validated as DN biomarkers.
  
  
  RESULTS
  We found urinary exosomalmiR-133b, miR-342, and miR-30a were expressed at significantly elevated levels in T2DN patients (P<0.001) compared to normal. Furthermore, high-level expression of the 3 miRNAs was associated withHbA1c,systolic-diastolic blood pressure, LDL, serum creatinine, urinary albumin creatinine ratio and estimated glomerular filtration rate(eGFR). Moreover, 39.3%, 19.6% and 17.9% of patients with normo-albuminuria had positive (miR-133b, miR-342 and miR-30a, respectively); indicating the possibility of molecular changes in these patients before onset of albuminuria.
  
  
  CONCLUSIONS
  We have identified novel urinary exosomal miRNA biomarkers of DN which were altered not only in micro and macroalbuminuric groups but also in some normoalbuminuria cases prior to albuminuria.
authors.affiliation: Oncology Diagnostic Unit, Medical Biochemistry and Molecular biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, P.O. Box 11381, Egypt. Electronic address: Dr_sanaa_eissa@yahoo.com.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Eissa
authors.affiliation: Oncology Diagnostic Unit, Medical Biochemistry and Molecular biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, P.O. Box 11381, Egypt. Electronic address: habiba20062001@yahoo.com.
authors.forename: Marwa
authors.initials: M
authors.lastname: Matboli
authors.affiliation: Diabetes and endocrinology Unit, Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Miram M
authors.initials: MM
authors.lastname: Bekhet
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D019295:Computational Biology / Q000379:methods*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology / Q000652:urine; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000652:urine*; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000652:urine*; D008875:Middle Aged; D012372:ROC Curve; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: Bioinformatics; Biomarkers; Diabetic nephropathy; Exosomes; Urine; miRNA