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Background and Objectives  Transcription factor 3 ( TCF3 ) implicates Wnt signaling pathway and regulates E-cadherin expression, which is involved in aggressiveness of tumors. This study aims to investigate the role of  TCF3  in predicting prognosis of patients with stage II and III colorectal cancer (CRC).    Methods  Real-Time quantitative PCR was performed in 64 fresh CRC tissues and 6 cell lines to examine  TCF3  mRNA expression. TCF3 protein expression dynamics were detected by immunohistochemistry of 118 paraffin-embedded specimens, and the clinical significance of TCF3 was assessed by clinical correlation and Kaplan-Meier analyses. Aberrant hypomethylation of  TCF3  promoter was also investigated using bisulfite sequencing and methylation specific PCR.    Results  The up-regulation of  TCF3  mRNA was frequently detected both in CRC tissues with recurrence and metastasis-derived cell lines. The expression level of TCF3 protein was significantly correlated with histological type ( P  = 0.038) and disease-free survival time ( P  = 0.002). Higher TCF3 expression indicated poor prognostic outcomes ( P <0.05, log-rank test). Multivariate analysis also showed strong TCF3 protein expression and perineural invasion were independent adverse prognosticators in CRC ( P  = 0.010, 0.000). Moreover, it was showed that promoter hypomethylation of  TCF3  is associated with its up-expression.    Conclusions  This study highlighted the prognostic value of  TCF3  in stage II and III CRC. The up-regulation of  TCF3 , which is mainly caused by promoter hypomethylation, is one of the molecular mechanisms involved in the development and progression of CRC.

Hypomethylation-Associated Up-Regulation of TCF3 Expression and Recurrence in Stage II and III Colorectal Cancer