guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, China.
Neoplasma. 2012;59(6):599-605. doi: 10.4149/neo_2012_076.
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.
转录因子 21（TCF21）已被鉴定为位于 6q23-q24 的候选肿瘤抑制因子，在许多类型的人类癌症中被表观遗传失活。我们最近发现 TCF21 甲基化水平在透明细胞肾细胞癌（ccRCC）中显著增加。本研究旨在探讨 TCF21 在 ccRCC 中的表达对预后的影响，并分析 TCF21 表达与甲基化水平之间的关系。我们使用实时 PCR 和免疫组织化学染色来检测 TCF21 的表达，并使用甲基化特异性-PCR（MS-PCR）来确定 ccRCC 样本和细胞系 786-O 中 TCF21 的甲基化状态。结果表明，ccRCC 样本中 TCF21 的表达水平明显低于正常相邻组织样本（NAT 样本）。Kaplan-Meier 生存分析表明，TCF21 是癌症特异性生存的显著预后因素（p=0.001）。此外，DNA 去甲基化剂 5'-氮杂胞苷通过抑制 786-O 中的 TCF21 甲基化，部分恢复了 TCF21 的表达。ccRCC 样本中 TCF21 的甲基化水平明显高于 NAT 样本。这些结果表明，TCF21 的表达是 ccRCC 患者生存不良的独立预后因素。异常甲基化是 TCF21 表达下调的重要原因，可能与 ccRCC 的发生有关。
