WWOX protein expression varies among RCC histotypes and downregulation of WWOX protein correlates with less-favorable prognosis in clear RCC

Ann Surg Oncol. 2013 Jan;20(1):193-9. doi: 10.1245/s10434-012-2371-x. Epub 2012 May 4.

Abstract

Background: WWOX has been shown to be a candidate tumor suppressor gene in numerous human cancers. The objective of this study is to determine the expression of WWOX in human renal cell carcinoma tumor cells and its possible correlation with clinical outcome.

Methods: The WWOX protein expressions of human renal cell carcinoma (RCC) tumor and of matched normal renal parenchyma were examined, and its correlation with clinical cancer-specific survival was investigated.

Results: Downregulation of WWOX only in clear cell type RCC was demonstrated in our results including immunohistochemistry, Western blot, and RT-PCR assay. For the remnant cell types of RCC, sample sizes were insufficient to draw any conclusion of WWOX protein expression. The decreased expression of WWOX in clear cell RCC tumor compared with matched normal renal parenchyma was also correlated with clinical cancer-specific survival (Kaplan-Meier, p=0.0482).

Conclusions: We proved that the expression level of WWOX is downregulated in human clear cell RCC. Moreover, the decreased expression of WWOX in clear cell RCC tumor compared with matched normal renal parenchyma was also correlated with clinical cancer-specific survival. Since clear cell RCC is a special human cancer using unique molecular pathogenesis, further investigation will provide more linking intracellular signaling of WWOX and novel therapeutic targets of human renal cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology*
  • Down-Regulation
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney / metabolism
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Prognosis
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • WW Domain-Containing Oxidoreductase

Substances

  • Tumor Suppressor Proteins
  • Oxidoreductases
  • WW Domain-Containing Oxidoreductase
  • WWOX protein, human