Abstract
Background and ObjectivesTranscription 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).MethodsReal-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.ResultsThe 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.ConclusionsThis 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.
Highlights
Colorectal cancer (CRC) is one of the three leading causes of cancer-related death among worldwide [1]
Transcription factor 3 gene (TCF3) expression was up-regulated in recurrent colorectal cancer (CRC) tissues and CRC- metastasis-derived cell lines
In 64 fresh samples, TCF3 mRNA expression was significantly higher in recurrent CRC tissues than in those without recurrence (P = 0.026; Figure 1a)
Summary
Colorectal cancer (CRC) is one of the three leading causes of cancer-related death among worldwide [1]. TCF3 is a ubiquitously expressed transcription regulator and encodes two basic helix-loop-helix (HLH) transcription factors, E12 and E47 [4]. These two proteins are characterized by broad expression pattern and ability to bind DNA [5,6,7,8]. As a transcriptional repressor of E-cadherin, TCF3 implicated in epithelial to mesenchymal transition and may be linked to tumor aggressiveness [14]. 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)
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