Downregulation of homeobox gene Barx2 increases gastric cancer proliferation and metastasis and predicts poor patient outcomes
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Yushuai Mi1,*, Senlin Zhao1,2,*, Chongzhi Zhou1, Junyong Weng1,*, Jikun Li1, Zhanshan Wang1, Huimin Sun3, Huamei Tang3, Xin Zhang4, Xiaofeng Sun2, Zhihai Peng1, Yugang Wen1,2
1Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China
2Department of Oncology and Department of Clinical and Experimental Medicine, Linkoping University, SE-581 85 Linkoping, Sweden
3Department of Pathology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China
4Department of Pathology, Zhejiang Provincial People’s Hospital, 310014 Hangzhou Zhejiang, China
*These authors have contributed equally to this work
Yugang Wen, email: firstname.lastname@example.org
Zhihai Peng, email: email@example.com
Keywords: gastric cancer, Barx2, progression, prognosis, Wnt/β-catenin
Received: May 14, 2016 Accepted: July 19, 2016 Published: August 12, 2016
Barx2 is a Bar family homeodomain transcription factor shown to play a critical role in cell adhesion and cytoskeleton remodeling, key processes in carcinogenesis and metastasis. Using quantitative real-time PCR, Western blotting, and immunohistochemistry, we found that Barx2 is expressed at lower levels in human gastric cancer (GC) tissues than in adjacent normal mucosa. In a multivariate analysis, Barx2 expression emerged as an independent prognostic factor for disease-free and overall survival. Kaplan-Meier survival analysis showed a trend toward even shorter overall survival in the patient group with Barx2-negative tumors, independent of advanced UICC stage and tumor relapse. Using in vitro and in vivo assays, we demonstrated that under normal conditions Barx2 inhibited GC cell proliferation and invasiveness through inhibition of the Wnt/β-catenin signaling pathway. These findings indicate that reduction or loss of Barx2 dis-inhibits GC cell proliferation and invasion, and that reduction in Barx2 could serve as an independent prognostic biomarker for poor outcome in GC patients.
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