title: Diagnostic and prognostic potential of differentially expressed miRNAs between metastatic and non-metastatic renal cell carcinoma at the time of nephrectomy.
abstract: BACKGROUND
  MicroRNAs are promising diagnostic and prognostic biomarkers in oncology. We aimed to evaluate the prognostic potential of selected microRNAs in primary clear cell renal cell carcinomas (ccRCC) as predictors of tumor recurrence after radical nephrectomy.
  
  
  METHODS
  miR-122, miR-141, miR-155, miR-184, miR-200c, miR-210, miR-224, and miR-514, validated as differentially expressed in a previous study, were measured by RT-PCR in matched malignant and non-malignant tumor samples after nephrectomy from 111 patients (89 without, 22 with metastases) and clinicopathological and outcome data were collected. Non-parametric statistical tests, receiver-operating characteristics, Kaplan-Meier-, and univariate as well as multivariate Cox regression analyses were performed.
  
  
  RESULTS
  Downregulation of miR-141/-184/-200c/-514 and upregulation of miR-122/-155/-210/-224 were not different between samples of non-metastatic and metastatic tumors except for miR-122 and miR-514. miR-514 was further downregulated in metastatic compared with non-metastatic tumors while the upregulation of miR-122 was significantly reduced in metastatic carcinomas. All miRNAs were suitable to discriminate malignant from non-malignant tissue. miR-122 and miR-514 were significantly related to the recurrence risk but only miR-514 provided independent prognostic information in the final model including relevant clinicopathological variables.
  
  
  CONCLUSIONS
  MiR-122 and miR-514 play a role in tumor recurrence after nephrectomy. Expression of miR-514 was particularly downregulated in primary metastatic tumor and those that recur and might be a suitable adjunct marker for predicting tumor recurrence.
authors.affiliation: Department of Urology, University Hospital Charité, Berlin, Germany.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Wotschofsky
authors.forename: Jonas
authors.initials: J
authors.lastname: Busch
authors.forename: Monika
authors.initials: M
authors.lastname: Jung
authors.forename: Carsten
authors.initials: C
authors.lastname: Kempkensteffen
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Schaser
authors.forename: Ingo
authors.initials: I
authors.lastname: Melcher
authors.forename: Ergin
authors.initials: E
authors.lastname: Kilic
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000503:physiopathology / Q000601:surgery; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009392:Nephrectomy; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012044:Regression Analysis
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs