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.
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.