title: Hsa-mir-124-3 CpG island methylation is associated with advanced tumours and disease recurrence of patients with clear cell renal cell carcinoma.
abstract: BACKGROUND
  Whether methylation of the microRNA (mir)-124-3 CpG island is of relevance for the clinical course of a solid cancer and whether it shows association with clinicopathology or survival of patients with renal cell cancer (RCC) is not known as yet.
  
  
  METHODS
  In a cross-sectional study, relative methylation of mir-124-3 was measured in 111 RCC samples and 77 paired normal appearing tissues using quantitative methyl-specific PCR. Results were statistically compared with tumour histology, clinicopathological parameters and disease recurrence.
  
  
  RESULTS
  We found tumour-specific hypermethylation of mir-124-3 in samples of RCCs with clear cell histology (ccRCC) compared with paired normal appearing tissues (P<0.0001). Methylation was significantly increased in tumours with state of advanced disease (P<0.0001). Higher relative methylation was associated with worse recurrence-free survival in both univariate (hazard ratio=9.37; P=0.0005) as well as bivariate Cox regression analyses considering age, sex, diameter of tumours and state of advanced disease, metastasis and lymph node metastases as covariates (hazard ratios=5.9-18.2; P-values of 0.0003-0.008).
  
  
  CONCLUSIONS
  We identified mir-124-3 CpG islands (CGI) methylation as a relevant epigenetic mark for ccRCC thus underlining the need for functional studies of potentially affected signalling pathways in kidney tumour models. Methylation of mir-124-3 is suggested as an independent prognosticator for ccRCC.
authors: Department of Urology, Hannover Medical School, OE6247, Carl-Neuberg-Str.1, 30625 Hannover, Germany.
authors: K
authors: K
authors: Gebauer
authors: I
authors: I
authors: Peters
authors: N
authors: N
authors: Dubrowinskaja
authors: J
authors: J
authors: Hennenlotter
authors: M
authors: M
authors: Abbas
authors: R
authors: R
authors: Scherer
authors: H
authors: H
authors: Tezval
authors: A S
authors: AS
authors: Merseburger
authors: A
authors: A
authors: Stenzl
authors: M A
authors: MA
authors: Kuczyk
authors: J
authors: J
authors: Serth
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D011379:Prognosis; D012008:Recurrence
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs