title: HOXA13 promotes cancer cell growth and predicts poor survival of patients with esophageal squamous cell carcinoma.
abstract: Homeobox genes are known to be classic examples of the intimate relationship between embryogenesis and tumorigenesis. Here, we investigated whether inhibition of HOXA13, a member of the homeobox genes, was sufficient to affect the proliferation of esophageal cancer cells in vitro and in vivo, and studied the association between HOXA13 expression and survival of patients with esophageal squamous cell carcinoma (ESCC). HOXA13 expression was permanently knocked down using an RNA interference technique, and cell strain with stable knockdown of HOXA13 protein was established. Colony formation assay showed that the number of colonies in HOXA13 protein-deficient cells was significantly less than that of control cells (P < 0.01). Tumor growth in nude mice showed that the weight and volume of tumors from the HOXA13 knockdown cells was significantly less than that from the control cells (P < 0.01). Then, HOXA13 expression in ESCC specimens and paired noncancerous mucosa was detected by immunohistochemistry, and overexpression of HOXA13 was found to be more pronounced in ESCCs than paired noncancerous mucosa (P < 0.05). Furthermore, the association of HOXA13 expression and disease-free survival time was analyzed in 155 ESCC cases. The median survival time of patients expressing HOXA13 was significantly shorter than HOXA13-negative patients (P = 0.0006). Multivariate analysis indicated that tumor-node-metastasis (TNM) stage and HOXA13 expression were independent predictors of disease-free survival time of patients with ESCC. Our results showed that HOXA13 expression enhanced tumor growth in vitro and in vivo, and was a negative independent predictor of disease-free survival of patients with ESCC.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, PR China.
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Gu
authors.forename: Lu-Yan
authors.initials: LY
authors.lastname: Shen
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Ning
authors.forename: Ke-Neng
authors.initials: KN
authors.lastname: Chen
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D034622:RNA Interference; D016019:Survival Analysis
chemical_list: D018398:Homeodomain Proteins; C099959:homeobox protein HOXA13