Carboplatin-gemcitabine combination chemotherapy upregulates AKR1B10 expression in bladder cancer

Int J Clin Oncol. 2013 Feb;18(1):177-82. doi: 10.1007/s10147-011-0363-7. Epub 2011 Dec 27.

Abstract

Background: AKR1B10 is considered to contribute to cell proliferation and chemoresistance. In the present study, we examined whether AKR1B10 expression is associated with disease-free survival in bladder cancer patients.

Methods: We obtained bladder cancer specimens from 10 patients before and after chemotherapy and measured AKR1B10 mRNA levels using real-time PCR. In addition, we conducted an immunohistochemical examination of AKR1B10 expression in 57 patients with bladder cancer before and after chemotherapy.

Results: AKR1B10 mRNA expression was significantly higher in the post-chemotherapy group than in the pre-chemotherapy group (p < 0.001). The average immunohistochemical intensity score in the pre-chemotherapy group was 0.83 ± 1.08, compared with the significantly higher score of 2.03 ± 1.03 in the post-chemotherapy group (p < 0.001). The disease-free survival rate of post-chemotherapy AKR1B10(+) patients (61.2%) was significantly lower than that of AKR1B10(-) patients (100%) (log-rank test, p = 0.039).

Conclusions: Although the present study is small and preliminary, our data suggest that post-chemotherapy AKR1B10 expression may be associated with a poor prognosis in patients who received carboplatin-gemcitabine combination chemotherapy and underwent cystectomy. Further study is warranted to elucidate its clinical significance.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aldehyde Reductase / genetics*
  • Aldo-Keto Reductases
  • Carboplatin / administration & dosage*
  • Cystectomy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Disease-Free Survival
  • Drug Therapy, Combination
  • Female
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery

Substances

  • Deoxycytidine
  • Carboplatin
  • AKR1B10 protein, human
  • Aldo-Keto Reductases
  • Aldehyde Reductase
  • Gemcitabine