title: Deregulated HOXB7 Expression Predicts Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma and Regulates Cancer Cell Proliferation In Vitro and In Vivo.
abstract: BACKGROUND
  We observed abnormal HOXB7 expression in esophageal squamous cell carcinoma (ESCC) previously. This study was to evaluate the prognostic significance of HOXB7 and reveal the potential mechanism.
  
  
  METHODS
  Immunohistochemistry was used to confirm the abnormal expression of HOXB7 in ESCC. The prognostic significance of HOXB7 expression was analyzed in two independent cohorts. RNAi was used to establish two stable HOXB7-knockdown cell strains. CCK8 assay, cell growth curve assay, colony formation assay, flow cycle analysis and tumorigenicity assay in nude mice were employed to investigate the effect of HOXB7 on proliferation in vitro and in vivo.
  
  
  RESULTS
  Immunohistochemistry confirmed the abnormal expression of HOXB7 in ESCC compared with paracancerous mucosa (18/23 vs. 9/23, p=0.039). HOXB7 expression was positively correlated with the T stage, lymph node metastasis and TNM stage. The median survival of patients with high HOXB7 expression was significantly shorter than that with low expression (45 months vs. 137 months, p = 0.007 for cohort 1; 19 months vs. 34 months, p = 0.001 for cohort 2). Multivariate survival analysis showed that HOXB7 expression was another independent prognostic factor (HR [95% CI] = 0.573 [0.341-0.963], p = 0.036 for cohort 1; HR [95%CI] = 0.543 [0.350-0.844], p = 0.024 for cohort 2). Experiments in vitro and in vivo showed that after knockdown of HOXB7, the proliferation rate dropped, growth rate descended, colony-formation ability reduced, G1-phase arrest occurred and the tumorigenicity reduced remarkably.
  
  
  CONCLUSIONS
  HOXB7 could promote cancer cell proliferation and might be an independent prognostic factor for patients with ESCC.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Lu-Yan
authors.initials: LY
authors.lastname: Shen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Wan-Pu
authors.initials: WP
authors.lastname: Yan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Xiao-Zheng
authors.initials: XZ
authors.lastname: Kang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dai
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Yong-Bo
authors.initials: YB
authors.lastname: Yang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Fu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: He-Li
authors.initials: HL
authors.lastname: Yang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Huang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Hong-Chao
authors.initials: HC
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Ke-Neng
authors.initials: KN
authors.lastname: Chen
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D064593:Heterografts; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D014408:Biomarkers, Tumor; C490538:HOXB7 protein, human; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering