Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Ann Surg Oncol. 2011 Oct;18(10):3005-12. doi: 10.1245/s10434-011-1653-z. Epub 2011 Apr 9.
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.
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.
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.
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.
配对同源盒转录因子 2（PITX2）基因编码一种转录因子，受结直肠癌（CRC）发病机制中 WNT/Dvl/CTNNB1 和 Hedgehog/TGFB 通路的调控。尽管 PITX2 据报道参与了多种功能，包括通过控制细胞生长来控制组织发育，但它在 CRC 中的意义尚不清楚。我们报告了关于人类 CRC 中异常 PITX2 表达的发现。
评估了 5 个人 CRC 细胞系和 92 个原发性 CRC 样本中的 PITX2 表达。抑制 PITX2 表达或外源性引入 PITX2 后，评估细胞生长。
在所有 5 个 CRC 细胞系中均观察到 PITX2 表达。组织样本研究表明，PITX2 表达在癌组织中明显高于配对对照组织（P = 0.0471）。PITX2 表达较低的患者总生存率低于 PITX2 表达较高的患者（P = 0.0481）。多变量分析表明，PITX2 表达是独立的预后因素。实验性敲低和引入 PITX2 也表明，PITX2 表达水平与体外细胞生长和侵袭呈负相关。
PITX2 表达与 CRC 细胞的生物学行为显著相关，似乎与临床生存相关。因此，本研究揭示了 PITX2 表达在 CRC 中以前未被描述的独特作用和意义。
