title: Expression of VEGF-D, SMAD4, and SMAD7 and Their Relationship with Lymphangiogenesis and Prognosis in Colon Cancer.
abstract: The vascular endothelial growth factor (VEGF) and TGF-β1 pathways play important roles in cancer. However, few studies have evaluated the expression and roles of VEGF-D, SMAD4, and SMAD7 in colon cancer, and the conclusions remain controversial. To clarify the roles of VEGF-D, SMAD4, and SMAD7 in colon cancer, we examined their expression and evaluated correlations with lymphangiogenesis, prognosis, and chemotherapeutic outcome.
  
  
  
  The expression of VEGF-D, SMAD4, and SMAD7 was immunohistochemically examined in 251 primary colon cancer samples obtained from the Harbin Medical University.
  
  
  
  The expression of VEGF-D, SMAD4, and SMAD7 was identified in 71.7, 41.0, and 69.7 % of samples, respectively. Positive expression of VEGF-D and SMAD7 and lost expression of SMAD4 were significantly correlated with lymph node metastasis and high lymphatic vessel density. VEGF-D and SMAD7 were found to be independent indicators of prognosis and chemotherapy outcome, and positive expression of either VEGF-D or SMAD7 was associated with significantly shorter overall survival and disease-free survival (OS and DFS) than negative expression in all 251 patients (P < 0.001 for OS and DFS) and patients following chemotherapy (P < 0.001 for OS and DFS).
  
  
  
  VEGF-D, SMAD4, and SMAD7 were involved in lymphangiogenesis and lymph node metastasis. VEGF-D and SMAD7 can serve as predictors of prognosis and chemotherapeutic outcome in colon cancer.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Su
authors.affiliation: Department of Anatomy, Harbin Medical University, 57 Baojian Road, Harbin, 150081, People's Republic of China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anatomy, Harbin Medical University, 57 Baojian Road, Harbin, 150081, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: You
authors.affiliation: Department of Anatomy, Harbin Medical University, 57 Baojian Road, Harbin, 150081, People's Republic of China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Harbin Medical University, 57 Baojian Road, Harbin, 150081, People's Republic of China.
authors.forename: Jianbing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Anatomy, Harbin Medical University, 57 Baojian Road, Harbin, 150081, People's Republic of China.
authors.forename: Yafang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Harbin Medical University, 57 Baojian Road, Harbin, 150081, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Anatomy, Harbin Medical University, 57 Baojian Road, Harbin, 150081, People's Republic of China. lbquan505@163.com.
authors.forename: Baoquan
authors.initials: B
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051901:Smad4 Protein / Q000378:metabolism*; D051906:Smad7 Protein / Q000378:metabolism*; D015996:Survival Rate; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C497796:SMAD4 protein, human; C497806:SMAD7 protein, human; D051901:Smad4 Protein; D051906:Smad7 Protein; C579459:VEGFD protein, human; D042643:Vascular Endothelial Growth Factor D
keywords: Colon cancer; Prognosis; SMAD4; SMAD7; VEGF-D