Gene expression signature in urine for diagnosing and assessing aggressiveness of bladder urothelial carcinoma

Clin Cancer Res. 2010 May 1;16(9):2624-33. doi: 10.1158/1078-0432.CCR-09-3373. Epub 2010 Apr 20.

Abstract

Purpose: To develop an accurate and noninvasive method for bladder cancer diagnosis and prediction of disease aggressiveness based on the gene expression patterns of urine samples.

Experimental design: Gene expression patterns of 341 urine samples from bladder urothelial cell carcinoma (UCC) patients and 235 controls were analyzed via TaqMan Arrays. In a first phase of the study, three consecutive gene selection steps were done to identify a gene set expression signature to detect and stratify UCC in urine. Subsequently, those genes more informative for UCC diagnosis and prediction of tumor aggressiveness were combined to obtain a classification system of bladder cancer samples. In a second phase, the obtained gene set signature was evaluated in a routine clinical scenario analyzing only voided urine samples.

Results: We have identified a 12+2 gene expression signature for UCC diagnosis and prediction of tumor aggressiveness on urine samples. Overall, this gene set panel had 98% sensitivity (SN) and 99% specificity (SP) in discriminating between UCC and control samples and 79% SN and 92% SP in predicting tumor aggressiveness. The translation of the model to the clinically applicable format corroborates that the 12+2 gene set panel described maintains a high accuracy for UCC diagnosis (SN = 89% and SP = 95%) and tumor aggressiveness prediction (SN = 79% and SP = 91%) in voided urine samples.

Conclusions: The 12+2 gene expression signature described in urine is able to identify patients suffering from UCC and predict tumor aggressiveness. We show that a panel of molecular markers may improve the schedule for diagnosis and follow-up in UCC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cluster Analysis
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis / methods
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / isolation & purification
  • RNA, Neoplasm / urine
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / urine
  • Urothelium / metabolism
  • Urothelium / pathology

Substances

  • RNA, Neoplasm