Bradeion (SEPT4) as a urinary marker of transitional cell bladder cancer: a real-time polymerase chain reaction study of gene expression

J Urol. 2012 Jun;187(6):2223-7. doi: 10.1016/j.juro.2012.01.031. Epub 2012 Apr 13.

Abstract

Purpose: We evaluated whether Bradeion/SEPT4 gene expression could be used as a potential urinary marker to diagnose bladder transitional cell carcinoma.

Materials and methods: From 2005 to 2007 we collected urine samples from 58 individuals, 17 healthy controls and 41 patients in whom bladder tumors were previously diagnosed by cystoscopy. Urine was collected from all patients before transurethral resection of bladder tumor. We performed real-time reverse transcriptase-polymerase chain reaction to evaluate Bradeion/SEPT4 transcript levels using urine sample mRNA. Statistical analysis was done with the Mann-Whitney test and ROC curves.

Results: Pathological examination of bladder tumor specimens revealed transitional cell bladder cancer. According to the 2002 TNM classification stage was Ta in 11 patients, T1 in 18 and T2/T3 in 12. All patients had G2 or G3 tumors according to the 1973 WHO grade classification. Relative quantification analysis of Bradeion transcript showed significantly increased levels compared to controls, namely 21.85 times higher in Ta stage tumors, 7.21 times higher in T1 tumors and 4.36 times higher in grade T2/T3 tumors. We compared each tumor stage group with the control group using the Mann-Whitney test to verify the statistical significance of observed differences. The ROC curve built on the change in threshold cycle revealed that with this method we attained 92.68% sensitivity and 64.71% specificity (AUC 0.798, p=0.0001).

Conclusions: Bradeion/SEPT4 transcript levels are significantly increased in patients with transitional cell bladder cancer compared to healthy controls. Our preliminary study supports the possible usefulness of Bradeion as a urinary marker of urothelial disease.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / urine
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / surgery
  • Carcinoma, Transitional Cell / urine
  • Female
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger
  • Real-Time Polymerase Chain Reaction
  • Septins / genetics
  • Septins / urine*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery
  • Urinary Bladder Neoplasms / urine
  • Urine / chemistry
  • Young Adult

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • SEPTIN4 protein, human
  • Septins