title: Role of thrombospondin-1 expression in colorectal liver metastasis and its molecular mechanism.
abstract: BACKGROUND
  Thrombospondin-1 (THBS-1), a glycoprotein, is an endogenous inhibitor of angiogenesis and tumor growth. In this study, we investigated the clinical role and mechanism of THBS-1 expression in colorectal liver metastases, focusing on the relationships between its expression and tumor growth, epithelial-mesenchymal transition (EMT), and expression of other relevant molecules.
  
  
  METHODS
  Ninety-four patients who initially underwent curative hepatic resection were enrolled in this study and correlations between expression of THBS-1 (THBS-1 high [n = 35] and THBS-1 low [n = 59]) and tumor growth, Ki-67 labeling index (Ki-67 LI), expression of other relevant molecules, and microvessel density (MVD) investigated.
  
  
  RESULTS
  THBS-1 low expression correlated with more advanced grade of liver and lymph node metastases and significantly worse overall survival than strong THBS-1 expression (3-year survival: 96.7% vs. 65.4%, P < 0.01). Multivariate analysis identified THBS-1 low expression as an independent prognostic factor (HR 2.82, 95% CI 1.21-7.71, P = 0.01). THBS-1 low expression correlated positively with high Ki-67 LI (P < 0.05) and inversely with E-cadherin (P < 0.05) and hypoxia inducible factor-1α (HIF-1α) expression (P < 0.05); THBS-1 expression and MVD were not significantly correlated.
  
  
  CONCLUSIONS
  Low THBS-1 expression may be an independent poor prognostic factor that affects tumor growth and EMT acquisition. Additionally, THBS-1 may be regulated by the HIF-1 pathway.
authors.affiliation: Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Teraoku
authors.affiliation: Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morine
authors.affiliation: Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
authors.affiliation: Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yoshikawa
authors.affiliation: Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Takasu
authors.affiliation: Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Higashijima
authors.affiliation: Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Imura
authors.affiliation: Department of Surgery, Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan. mitsuo.shimada@tokushima-u.ac.jp.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001707:Biopsy, Needle; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy / Q000379:methods / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies; D012380:Role; D016019:Survival Analysis; D019700:Thrombospondin 1 / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019700:Thrombospondin 1
keywords: Colorectal liver metastasis; Immunohistochemistry; Thrombospondin-1