title: Downregulation of homeobox gene Barx2 increases gastric cancer proliferation and metastasis and predicts poor patient outcomes.
abstract: 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.
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China.
authors.forename: Yushuai
authors.initials: Y
authors.lastname: Mi
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China.|Department of Oncology and Department of Clinical and Experimental Medicine, Linkoping University, SE-581 85 Linkoping, Sweden.
authors.forename: Senlin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China.
authors.forename: Chongzhi
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China.
authors.forename: Junyong
authors.initials: J
authors.lastname: Weng
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China.
authors.forename: Jikun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China.
authors.forename: Zhanshan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pathology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China.
authors.forename: Huamei
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Pathology, Zhejiang Provincial People's Hospital, 310014 Hangzhou Zhejiang, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Oncology and Department of Clinical and Experimental Medicine, Linkoping University, SE-581 85 Linkoping, Sweden.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 200080 Shanghai, China.|Department of Oncology and Department of Clinical and Experimental Medicine, Linkoping University, SE-581 85 Linkoping, Sweden.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wen
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis; D002448:Cell Adhesion; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D063868:Patient Outcome Assessment; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D016019:Survival Analysis; D046888:Tissue Array Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: C491320:BARX2 protein, human; D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins
keywords: Barx2; Wnt/β-catenin; gastric cancer; prognosis; progression