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PITX2: a promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma.

Abstract：

:The paired-like homeodomain transcription factor 2 (PITX2), a downstream effector of wnt/β-catenin signaling, is well known to play critical role during normal embryonic development. However, the possible involvement of PITX2 in human tumorigenesis remains unclear. In this study, we extend its function in human esophageal squamous cell carcinoma (ESCC). The real-time PCR, Western blotting and immunohistochemistry (IHC) methods were applied to examine expression pattern of PITX2 in two different cohorts of ESCC cases treated with definitive chemoradiotherapy (CRT). Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff point for PITX2 high expression in the training cohort. The ROC-derived cutoff point was then subjected to analyze the association of PITX2 expression with patients' survival and clinical characteristics in training and validation cohort, respectively. The expression level of PITX2 was significantly higher in ESCCs than that in normal esophageal mucosa. There was a positive correlation between PITX2 expression and clinical aggressiveness of ESCC. Importantly, high expression of PITX2 was observed more frequently in CRT resistant group than that in CRT effective group (p < 0.05). Furthermore, high expression of PITX2 was associated with poor disease-specific survival (p < 0.05) in ESCC. Then, the MTS, clonogenic survival fraction and cell apoptosis experiments showed that knockdown of PITX2 substantially increased ESCC cells sensitivity to ionizing radiation (IR) or cisplatin in vitro. Thus, the expression of PITX2, as detected by IHC, may be a useful tool for predicting CRT resistance and serves as an independent molecular marker for poor prognosis of ESCC patients treated with definite CRT.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Zhang JX,Tong ZT,Yang L,Wang F,Chai HP,Zhang F,Xie MR,Zhang AL,Wu LM,Hong H,Yin L,Wang H,Wang HY,Zhao Y

doi

10.1002/ijc.27930

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

2567-77

issue

eissn

0020-7136

issn

1097-0215

journal_volume

132

pub_type

杂志文章

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PITX2: a promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma.