Purpose: The paired-like homeodomain transcription factor 2 (PITX2) gene encodes a transcription factor controlled by the WNT/Dvl/CTNNB1 and Hedgehog/TGFB pathways in the pathogenesis of colorectal cancer (CRC). Although PITX2 is reportedly involved in various functions, including tissue development by controlling cell growth, its significance in CRC remains unclear. We report our findings regarding abnormal PITX2 expression in human CRC. Methods: PITX2 expression was evaluated in 5 human CRC cell lines and 92 primary CRC samples. Cell growth was evaluated after inhibition of PITX2 expression or after exogenous introduction of PITX2. Results: PITX2 expression was seen in all the five CRC cell lines. The study of tissue samples indicated that PITX2 expression was significantly higher in cancerous tissue than in paired control tissue (P = 0.0471). Patients with lower PITX2 expression showed a poorer overall survival rate than those with higher PITX2 expression (P = 0.0481). Multivariate analysis demonstrated that PITX2 expression was an independent prognostic factor. Experimental knockdown and introduction of PITX2 also demonstrated that the level of PITX2 expression is inversely associated with cell growth and invasion in vitro. Conclusions: PITX2 expression is significantly related to the biological behavior of CRC cells and appears to be correlated with clinical survival. Thus, this study revealed a previously uncharacterized unique role and significance of PITX2 expression in CRC.
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