Gene expression study of Aurora-A reveals implication during bladder carcinogenesis and increasing values in invasive urothelial cancer

Urology. 2008 Oct;72(4):873-7. doi: 10.1016/j.urology.2007.12.026. Epub 2008 May 15.

Abstract

Objectives: Urothelial carcinoma is a frequent and aggressive cancer. We wanted to gain better insight into the early molecular mechanisms of bladder carcinogenesis by evaluating Aurora-A gene expression, which is implicated in genomic stability and essential for mitosis.

Materials: This study, using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), analyzed the expression levels of three selected genes in dissected tissues from normal bladder, noninvasive cancers, and muscle-invasive bladder carcinomas (n = 49). We compared gene expression levels of three genes (Aurora-A, and as control uroplakin II (UPII) and TBP, respectively) at different stages of bladder cancer. We used multivariate analysis, receiver operating characteristic curves and the nonparametric Mann-Whitney test.

Results: The expression of Aurora-A gene studied was significantly deregulated, with an increasing level in cancer versus normal tissue Aurora-A. This development was linear. Aurora-A was already deregulated in early stages of carcinogenesis (pTa/pT1) (P = 0.0004) and displayed even more deregulation in muscle-invasive stages (pT2 to pT4). Immunohistochemistry performed on the same samples using Aurora-A antibody confirmed results of RT-PCR, with statistically significant values when comparing m-RNA expression and immunohistochemical values (P = 0.0001).

Conclusions: This study highlights the fact that Aurora-A gene expression is already strongly deregulated in early stages of urothelial carcinoma with abnormal expression, and might be considered a biomarker of tumor aggression. The increase in Aurora-A expression might provide further information regarding the behavior of bladder cancer in daily practice.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aurora Kinases
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Protein-Serine-Threonine Kinases / genetics*
  • RNA, Messenger / analysis
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*
  • Urothelium / pathology

Substances

  • RNA, Messenger
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases