title: MicroRNA profiling in clear cell renal cell carcinoma tissues potentially links tumorigenesis and recurrence with obesity.
abstract: Twenty to 40% localised RCC patients may experience recurrence after curative surgery. Limited miRNA predictors have been identified for ccRCC recurrence.
  
  
  
  Through a multi-phase study design, we analysed miRNAs in tissues obtained from 203 ccRCC patients. Paired t-test was used for tumour-normal comparisons and Cox regression model was performed to compute hazard ratios (HRs) and corresponding 95% CIs.
  
  
  
  A 17-miRNA signature was identified that can concordantly classify >95% of tumour/adjacent normal samples. Significant enrichment was found as 6 out of 17 miRNAs were associated with obesity (binomial probability=0.001). Decreased levels of miR-204-5p and miR-139-5p were each associated with an approximately three-fold increased risk of recurrence (P<0.01). Risk score was generated based on expressions of miR-204-5p and miR-139-5p, and the trend test was significant in both discovery and validation sets (Pfor trend<0.05). Striking MST reduction was observed for patients with a high-risk score (high vs low: discovery, 9.4 vs >97.7 months; validation, 20.8 vs >70.3 months). Expressions of miR-204-5p were also associated with body mass index (β=5.64, P<0.001). Significant inverse correlations were observed and validated between miR-204-5p and 13 obesity-related genes (r<0, P<0.01).
  
  
  
  We identified 17 miRNAs dysregulated in ccRCC tissues and showed that low expressions of miR-204-5p and miR-139-5p were associated with the higher risk of recurrence. The link between miR-204-5p and ccRCC recurrence may be partially mediated by regulating the expression of targeted obesity-related genes.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: X
authors.initials: X
authors.lastname: Shu
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Hildebrandt
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Tannir
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Matin
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Karam
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Wood
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wu
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009765:Obesity / Q000150:complications / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D035683:MicroRNAs