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Hypomethylation-associated up-regulation of TCF3 expression and recurrence in stage II and III colorectal cancer.

Li C, Cai S, Wang X, Jiang Z - PLoS ONE (2014)

Bottom Line: Higher TCF3 expression indicated poor prognostic outcomes (P<0.05, log-rank test).Moreover, it was showed that promoter hypomethylation of TCF3 is associated with its up-expression.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China.

ABSTRACT

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.

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Related in: MedlinePlus

Representatives of TCF3 expression in stage II and III CRC tissues detected by immunohistochemistry.Examples of the immunostaining of TCF3 at strong expression (a, b) and low expression (c, d) levels (magnification ×400).
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pone-0112005-g002: Representatives of TCF3 expression in stage II and III CRC tissues detected by immunohistochemistry.Examples of the immunostaining of TCF3 at strong expression (a, b) and low expression (c, d) levels (magnification ×400).

Mentions: Positive staining was observed primarily in cytoplasm and nuclear of the cancer cells. Analysis of TCF3 expression in the 118 CRC tissues revealed that 37% of samples demonstrating strong (2+ and 3+) intensities and 63% low (− and +) intensities. Immunostaining of TCF3 protein is illustrated in Figure 2.


Hypomethylation-associated up-regulation of TCF3 expression and recurrence in stage II and III colorectal cancer.

Li C, Cai S, Wang X, Jiang Z - PLoS ONE (2014)

Representatives of TCF3 expression in stage II and III CRC tissues detected by immunohistochemistry.Examples of the immunostaining of TCF3 at strong expression (a, b) and low expression (c, d) levels (magnification ×400).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4222969&req=5

pone-0112005-g002: Representatives of TCF3 expression in stage II and III CRC tissues detected by immunohistochemistry.Examples of the immunostaining of TCF3 at strong expression (a, b) and low expression (c, d) levels (magnification ×400).
Mentions: Positive staining was observed primarily in cytoplasm and nuclear of the cancer cells. Analysis of TCF3 expression in the 118 CRC tissues revealed that 37% of samples demonstrating strong (2+ and 3+) intensities and 63% low (− and +) intensities. Immunostaining of TCF3 protein is illustrated in Figure 2.

Bottom Line: Higher TCF3 expression indicated poor prognostic outcomes (P<0.05, log-rank test).Moreover, it was showed that promoter hypomethylation of TCF3 is associated with its up-expression.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus