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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 10/2011

01-10-2011 | Healthcare Policy and Outcomes

The Significance of PITX2 Overexpression in Human Colorectal Cancer

Authors: Hajime Hirose, MD, Hideshi Ishii, MD, PhD, Koshi Mimori, MD, PhD, Fumiaki Tanaka, MD, PhD, Ichiro Takemasa, MD, PhD, Tsunekazu Mizushima, MD, PhD, Masataka Ikeda, MD, PhD, Hirofumi Yamamoto, MD, PhD, Mitsugu Sekimoto, MD, PhD, Yuichiro Doki, MD, PhD, Masaki Mori, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 10/2011

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Abstract

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.
Appendix
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Metadata
Title
The Significance of PITX2 Overexpression in Human Colorectal Cancer
Authors
Hajime Hirose, MD
Hideshi Ishii, MD, PhD
Koshi Mimori, MD, PhD
Fumiaki Tanaka, MD, PhD
Ichiro Takemasa, MD, PhD
Tsunekazu Mizushima, MD, PhD
Masataka Ikeda, MD, PhD
Hirofumi Yamamoto, MD, PhD
Mitsugu Sekimoto, MD, PhD
Yuichiro Doki, MD, PhD
Masaki Mori, MD, PhD, FACS
Publication date
01-10-2011
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 10/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-1653-z

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