Protein expression and promoter methylation of the candidate biomarker TCF21 in gastric cancer.

Abstract

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. This study aimed to determine the expression of TCF21 mRNA and protein in gastric cancer cell lines and tissue specimens and then investigate the prognostic impact of TCF21 expression in gastric cancer 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 to determine the methylation status of TCF21 in gastric cancer samples and gastric cancer cell lines. The results showed that TCF21 expression level in gastric cancer samples was significantly lower than in normal adjacent tissue samples. The Kaplan-Meier survival analysis demonstrated that TCF21 was a significant prognosticator of cancer-specific survival (p = 0.001). Furthermore, the methylation level of TCF21 in gastric cancer samples was much higher than the samples in normal adjacent tissue. Treatment with the DNA methyltransferase inhibitor 5-Aza-2'-deoxy-cytidine can upregulate the expression of TCF21 in gastric cancer cells. These results suggest that the low expression of TCF21 was an independent prognostic factor for poor survival in patients with gastric cancer. Aberrant methylation was an important reason for the downregulation of TCF21 and may be associated with tumorigenesis in gastric cancer.