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CpG Hypermethylation of the UCHL1 Gene Promoter is Associated With Pathogenesis and Poor Prognosis in Renal Cell Carcinoma.
- Source :
- Journal of Urology; Jul2008, Vol. 180 Issue 1, p343-351, 9p
- Publication Year :
- 2008
-
Abstract
- Purpose: Aberrant DNA hypermethylation has been reported in renal cell carcinoma. We performed microarray analysis in the renal cancer cell line ACHN treated with the demethylating agent 5-aza-2′-deoxycytidine and investigated the UCHL1 gene involved in the regulation of cellular ubiquitin levels. Materials and Methods: We subjected 131 renal cell carcinoma and 61 corresponding normal kidney tissue samples to real-time reverse transcriptase-polymerase chain reaction, quantitative methylation specific polymerase chain reaction and immunohistochemistry. We also established a stable UCHL1 transfectant to evaluate cell growth. Results: We identified 10 genes that were up-regulated more than 2.5-fold in 5-aza-2′-deoxycytidine treated vs untreated ACHN cells. UCHL1 expression was increased 3.41-fold by 5-aza-2′-deoxycytidine treatment. In clinical samples the UCHL1 methylation index was significantly higher in renal cell carcinoma than in normal kidney tissue (p = 0.011). Conversely UCHL1 mRNA expression was significantly lower in renal cell carcinoma than in normal kidney tissue (p <0.0001). There was a negative correlation between mRNA expression and the UCHL1 methylation index (p = 0.017). The immunostaining score for UCHL1 was significantly higher in normal kidney tissue than in renal cell carcinoma (p <0.0001). Kaplan-Meier analysis showed that a positive UCHL1 methylation index had a significant adverse effect on prognosis (p = 0.048). Significant growth inhibition in UCHL1 transfectant compared to that in WT ACHN (p <0.0001) suggests that UCHL1 functions as a potential tumor suppressor gene in human renal cell carcinoma. Conclusions: To our knowledge we report the first study demonstrating that the mechanism of UCHL1 down-regulation in renal cell carcinoma is through CpG hypermethylation of the promoter region and methylation of the UCHL1 gene is associated with a poor prognosis in patients with renal cell carcinoma. [Copyright &y& Elsevier]
- Subjects :
- CANCER prognosis
RENAL cancer
RENAL cell carcinoma
DEHYDROGENASES
Subjects
Details
- Language :
- English
- ISSN :
- 00225347
- Volume :
- 180
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Journal of Urology
- Publication Type :
- Academic Journal
- Accession number :
- 32559186
- Full Text :
- https://doi.org/10.1016/j.juro.2008.02.044