title: Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma.
abstract: BACKGROUND
  There is no standard serum biomarker used for diagnosis or early detection of recurrence for renal cell carcinoma (RCC) patients. MicroRNAs (miRNAs) are abundant and highly stable in blood serum, and have been recently described as powerful circulating biomarkers in a wide range of solid cancers. Our aim was to identify miRNA signature that can distinguish the blood serum of RCC patients and matched healthy controls and validate identified miRNAs as potential biomarkers for RCC.
  
  
  METHODS
  In the screening phase of the study, blood serum of 15 RCC patients and 12 matched healthy controls were analyzed by use of the TaqMan Low-Density Arrays enabling parallel identification of expression levels of 667 miRNAs through qRT-PCR-based approach. In the validation phase, identified miRNAs were further evaluated on the independent group of 90 RCC patients and 35 matched healthy controls by use of individual qRT-PCR assays and statistically evaluated.
  
  
  RESULTS
  We identified 30 miRNAs differentially expressed between serum of RCC patients and healthy controls: 19 miRNAs were up-regulated and 11 miRNAs were down-regulated in RCC patients. MiR-378, miR-451 and miR-150 were further evaluated in the independent group of patients, and two of them were successfully validated: levels of miR-378 were increased (p = 0.0003, AUC = 0.71), miR-451 levels were decreased (p < 0.0001, AUC = 0.77) in serum of RCC patients. Combination of miR-378 and miR-451 enable identification of RCC serum with the sensitivity of 81%, specificity 83% and AUC = 0.86.
  
  
  CONCLUSIONS
  Circulating miRNAs in serum are promising biomarkers in RCC.
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Redova
authors.forename: Alexandr
authors.initials: A
authors.lastname: Poprach
authors.forename: Jana
authors.initials: J
authors.lastname: Nekvindova
authors.forename: Robert
authors.initials: R
authors.lastname: Iliev
authors.forename: Lenka
authors.initials: L
authors.lastname: Radova
authors.forename: Radek
authors.initials: R
authors.lastname: Lakomy
authors.forename: Marek
authors.initials: M
authors.lastname: Svoboda
authors.forename: Rostislav
authors.initials: R
authors.lastname: Vyzula
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slaby
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008403:Mass Screening; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D012372:ROC Curve; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; C526012:MIRN378 microRNA, human; C531201:MIRN451 microRNA, human; D035683:MicroRNAs