Korean J Urol.  2013 Sep;54(9):631-637.

Decreased DBC1 Expression Is Associated With Poor Prognosis in Patients With Non-Muscle-Invasive Bladder Cancer

Affiliations
  • 1Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea. wtkimuro@chungbuk.ac.kr
  • 2The Urological Diseases Research Center, Children's Hospital Boston, Boston, MA, USA.
  • 3Departments of Surgery and Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
  • 4Section of Urologic Oncology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
  • 5Database/Bioinformatics Laboratory, Chungbuk National University, Cheongju, Korea.
  • 6Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Korea.
  • 7Department of Food and Biotechnology, Chungang University, Seoul, Korea.

Abstract

PURPOSE
The deleted in bladder cancer 1 (DBC1) gene is located within chromosome 9 (9q32-33), a chromosomal region that frequently shows loss of heterozygosity in bladder cancer (BC). It is suspected that it acts as a tumor suppressor gene, but its prognostic value remains unclear. The aim of the present study was to investigate the value of DBC1 as a prognostic marker in BC.
MATERIALS AND METHODS
The expression of DBC1 was determined by real-time polymerase chain reaction analysis in 344 patients with BC (220 non-muscle-invasive BC [NMIBC] and 124 muscle-invasive BC [MIBC]) and in 34 patients with normal bladder mucosa. The results were compared with clinicopathologic parameters, and the prognostic value of DBC1 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model.
RESULTS
DBC1 expression was significantly decreased in patients with MIBC compared with those diagnosed with NMIBC (p=0.010). Patients with aggressive tumor characteristics had lower DBC1 expression levels in NMIBC (each, p<0.05). By multivariate Cox regression analysis, low DBC1 expression was a predictor of progression to MIBC (hazard ratio, 7.104; p=0.013). Kaplan-Meier estimates revealed a significant difference in tumor recurrence, progression to MIBC, and cancer-specific survival depending on the level of DBC1 expression in NMIBC (log-rank test, each, p<0.05).
CONCLUSIONS
The expression of DBC1 was associated with tumor aggressiveness, progression to MIBC, and survival in NMIBC. Our results suggest that DBC1 expression can be a useful prognostic marker for patients with NMIBC.

Keyword

Bladder cancer; Human DBC1 protein; Prognosis

MeSH Terms

Chromosomes, Human, Pair 9
Genes, Tumor Suppressor
Humans
Kaplan-Meier Estimate
Loss of Heterozygosity
Mucous Membrane
Prognosis
Real-Time Polymerase Chain Reaction
Recurrence
Urinary Bladder
Urinary Bladder Neoplasms

Figure

  • FIG. 1 The probability of (A) recurrence, (B) progression to muscle invasive bladder cancer, and (C) cancer specific survival according to DBC1 mRNA expression levels. Cutoff value was 35.5×104 copies per mg.


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