title: Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma.
abstract: BACKGROUND
  Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs.
  
  
  METHODS
  Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC).
  
  
  RESULTS
  RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease.
  
  
  CONCLUSIONS
  A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.
authors.affiliation: Department of Urology and Paediatric Urology, Julius-Maximilians-University Medical Centre of Würzburg, Würzburg, Germany. vergho_d@klinik.uni-wuerzburg.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vergho
authors.forename: Susanne
authors.initials: S
authors.lastname: Kneitz
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Charlotte
authors.initials: C
authors.lastname: Scherer
authors.forename: Martin
authors.initials: M
authors.lastname: Spahn
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.forename: Hubertus
authors.initials: H
authors.lastname: Riedmiller
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kneitz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009392:Nephrectomy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C527111:MIRN126 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs