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

被引:44
|
作者
Zhang, Jia-Xing [1 ,2 ]
Tong, Zhu-Ting [1 ]
Yang, Lin [1 ]
Wang, Fan [1 ]
Chai, Hui-Ping [3 ]
Zhang, Fan [1 ]
Xie, Ming-Ran [4 ]
Zhang, An-Li [5 ]
Wu, Li-Ming [1 ]
Hong, Hao [1 ]
Yin, Lv [1 ]
Wang, Hao [1 ]
Wang, Hong-Yan [1 ]
Zhao, Yuan [3 ]
机构
[1] Anhui Med Univ, Affiliated Hosp 1, Dept Radiotherapy, Hefei 230022, Peoples R China
[2] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol Southern China, Guangzhou 510275, Guangdong, Peoples R China
[3] Anhui Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Hefei 230022, Peoples R China
[4] Anhui Med Univ, Anhui Prov Hosp, Dept Thorac Surg, Hefei 230022, Peoples R China
[5] Anhui Med Univ, Anhui Prov Hosp, Dept Pathol, Hefei 230022, Peoples R China
关键词
esophageal squamous cell carcinoma; PITX2; chemoradiotherapy; immunohistochemistry; BREAST-CANCER PATIENTS; EPITHELIAL-MESENCHYMAL TRANSITION; BETA-CATENIN/TCF PATHWAY; LEFT-RIGHT ASYMMETRY; DNA-METHYLATION; GENE-EXPRESSION; PITUITARY; CHEMORADIATION; MULTICENTER; OVEREXPRESSION;
D O I
10.1002/ijc.27930
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The paired-like homeodomain transcription factor 2 (PITX2), a downstream effector of wnt/-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.
引用
收藏
页码:2567 / 2577
页数:11
相关论文
共 50 条
  • [31] Lymphopenia Predicts Poor Prognosis in Patients With Esophageal Squamous Cell Carcinoma
    Feng, Ji-Feng
    Liu, Jin-Shi
    Huang, Ying
    MEDICINE, 2014, 93 (27)
  • [32] Slug Is a Predictor of Poor Prognosis in Esophageal Squamous Cell Carcinoma Patients
    Hasan, Md Raghibul
    Sharma, Rinu
    Saraya, Anoop
    Chattopadhyay, Tushar K.
    DattaGupta, Siddartha
    Walfish, Paul G.
    Chauhan, Shyam S.
    Ralhan, Ranju
    PLOS ONE, 2013, 8 (12):
  • [33] H3K27me3 Protein Is a Promising Predictive Biomarker of Patients’ Survival and Chemoradioresistance in Human Nasopharyngeal Carcinoma
    Mu-Yan Cai
    Zhu-Ting Tong
    Wei Zhu
    Zhu-Zhi Wen
    Hui-Lan Rao
    Ling-Ling Kong
    Xin-Yuan Guan
    Hsiang-Fu Kung
    Yi-Xin Zeng
    Dan Xie
    Molecular Medicine, 2011, 17 : 1137 - 1145
  • [34] ORAOV1 overexpression in esophageal squamous cell carcinoma and esophageal dysplasia: a possible biomarker of progression and poor prognosis in esophageal carcinoma
    Li, Man
    Cui, Xiaobin
    Shen, Yaoyuan
    Dong, Hongchao
    Liang, Weihua
    Chen, Yunzhao
    Hu, Jianming
    Li, Shugang
    Kong, Ling
    Li, Hongan
    Zhao, Jin
    Li, Feng
    HUMAN PATHOLOGY, 2015, 46 (05) : 707 - 715
  • [35] Serum microRNA-193b as a promising biomarker for prediction of chemoradiation sensitivity in esophageal squamous cell carcinoma patients
    Chan, Chung Man
    Lai, Kenneth K. Y.
    Ng, Enders K. O.
    Kiang, Mei Na
    Kwok, Tiffany W. H.
    Wang, Hector K.
    Chan, Kwok Wah
    Law, Tsz Ting
    Tong, Daniel K.
    Chan, Kin Tak
    Lee, Nikki P.
    Law, Simon
    ONCOLOGY LETTERS, 2018, 15 (03) : 3273 - 3280
  • [36] BC200 LncRNA a potential predictive marker of poor prognosis in esophageal squamous cell carcinoma patients
    Zhao, Rui-Hua
    Zhu, Cai-Hua
    Li, Xiang-Ke
    Cao, Wei
    Zong, Hong
    Cao, Xin-Guang
    Hu, Hai-Yan
    ONCOTARGETS AND THERAPY, 2016, 9 : 2221 - 2226
  • [37] Tumor-infiltrating plasma cells are the promising prognosis marker for esophageal squamous cell carcinoma
    Yao, Chengyun
    Yu, Hongliang
    Zhou, Guoren
    Xu, Jianhua
    Gu, Dayong
    Yin, Li
    He, Xia
    Xia, Hongping
    ESOPHAGUS, 2021, 18 (03) : 574 - 584
  • [38] Tumor-infiltrating plasma cells are the promising prognosis marker for esophageal squamous cell carcinoma
    Chengyun Yao
    Hongliang Yu
    Guoren Zhou
    Jianhua Xu
    Dayong Gu
    Li Yin
    Xia He
    Hongping Xia
    Esophagus, 2021, 18 : 574 - 584
  • [39] Promising outcomes of definitive chemoradiation and cetuximab for patients with esophageal squamous cell carcinoma
    Chen, Yongshun
    Wu, Xiaoyuan
    Bu, Shanshan
    He, Chunyu
    Wang, Wen
    Liu, Jinsong
    Guo, Wei
    Tan, Bo
    Wang, Yanxia
    Wang, Jianhua
    CANCER SCIENCE, 2012, 103 (11) : 1979 - 1984
  • [40] H3K27me3 Protein Is a Promising Predictive Biomarker of Patients' Survival and Chemoradioresistance in Human Nasopharyngeal Carcinoma
    Cai, Mu-Yan
    Tong, Zhu-Ting
    Zhu, Wei
    Wen, Zhu-Zhi
    Rao, Hui-Lan
    Kong, Ling-Ling
    Guan, Xin-Yuan
    Kung, Hsiang-Fu
    Zeng, Yi-Xin
    Xie, Dan
    MOLECULAR MEDICINE, 2011, 17 (11-12) : 1137 - 1145