Down-regulation of TCF21 is associated with poor survival in clear cell renal cell carcinoma.

Transcription factor 21 (TCF21) has been identified as a candidate tumor suppressor at 6q23-q24 that is epigenetically inactivated in many types of human cancers. We recently found that TCF21 methylation level was significantly increased in clear cell renal cell carcinoma (ccRCC). The purpose of this study was to investigate the prognostic impact of TCF21 expression in ccRCC and analyze the relationship between TCF21 expression and methylation level. We used real-time PCR and immunohistochemical staining to detect the expression of TCF21, and used methylation specific-PCR (MS-PCR) to determine the methylation status of TCF21 in ccRCC samples and cell line 786-O. The results showed that TCF21 expression level in ccRCC samples was significantly lower than in normal adjacent tissue samples (NAT samples). The Kaplan-Meier survival analysis demonstrated that TCF21 was a significant prognosticator of cancer-specific survival (p=0.001). Furthermore, the DNA demethylating agent 5'-azacytidine restored part of TCF21 expression by suppressing TCF21 methylation in 786-O. The methylation level of TCF21 in ccRCC samples was much higher than in NAT samples. These results suggest that the expression of TCF21 was an independent prognostic factor for poor survival in patients with ccRCC. Aberrant methylation was an important reason for the down-regulation the expression of TCF21, and may be associated with tumorigenesis in ccRCC.