title: The miR(21/10b) ratio as a prognostic marker in clear cell renal cell carcinoma.
abstract: OBJECTIVE
  Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer in the adult kidney, and the prognosis of metastatic ccRCC remains poor with high mortality. In ccRCC, microRNAs (miRs) differentially expressed in tumour tissue have been identified and have been proposed to predict prognosis. The purpose of this study was to evaluate candidate miR markers identified from analysis of The Cancer Genome Atlas (TCGA) datasets in a large RCC cohort and to elucidate whether a ratio of miRs provided additional prognostic information.
  
  
  METHODS
  Deep sequencing data from TCGA datasets were analysed using biostatistical methods to identify candidate miRs that correlate with factors such as survival and stage of disease. Candidate miRs were analysed by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) in a cohort of 198 RCC tumours (ccRCC, n=152) and 50 normal kidney samples.
  
  
  RESULTS
  Four candidate miRs (miR-10b, miR-21, miR-101 and miR-223) were selected from the TCGA analysis and analysed in our cohort. Of these, miR-21 and miR-10b were differentially expressed in RCC subtypes and in ccRCC nuclear grades. Individually, the two miRs demonstrated a non-significant trend to correlate with survival. Importantly, the ratio of miR-21/miR10b (miR(21/10b)) correlated significantly with disease severity and survival, a high miR(21/10b) being associated with poor prognosis (P=0.0095). In particular, the miR(21/10b) was found to be an independent prognostic factor in metastasis-free patients (P=0.016; confidence interval (CI) 1.201-5.736).
  
  
  CONCLUSIONS
  We have shown that the miR(21/10b) ratio is an independent prognostic factor for M0 ccRCC patients, which could be useful to identify high-risk M0 patients who could benefit from increased surveillance.
authors.affiliation: Lund University, Department of Laboratory Medicine, Section of Clinical Chemistry, University Hospital Malmö, Malmö, Sweden.
authors.forename: Helena K M
authors.initials: HKM
authors.lastname: Fritz
authors.affiliation: Lund University, Department of Laboratory Medicine, Section of Molecular Tumor Biology, Medicon Village, Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Lindgren
authors.affiliation: Umeå University, Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå, Sweden.
authors.forename: Börje
authors.initials: B
authors.lastname: Ljungberg
authors.affiliation: Lund University, Department of Laboratory Medicine, Section of Molecular Tumor Biology, Medicon Village, Lund, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Axelson
authors.affiliation: Lund University, Department of Laboratory Medicine, Section of Clinical Chemistry, University Hospital Malmö, Malmö, Sweden. Electronic address: Bjorn.Dahlback@med.lu.se.
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlbäck
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D016022:Case-Control Studies; D030541:Databases, Genetic; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010641:Phenotype; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; C547183:MIRN10 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs
keywords: Biomarker; Cancer; Clear cell renal cell carcinoma; Kidney cancer; Prognosis; RCC; Renal cancer; miRNA; microRNA