title: Prognostic significance of VEGF-C, semaphorin 3F, and neuropilin-2 expression in oral squamous cell carcinomas and their relationship with lymphangiogenesis.
abstract: BACKGROUND
  Neuropilin-2 (NRP2), a receptor for vascular endothelial growth factor C (VEGF-C) and semaphorin 3 F (SEMA3F), is a possible regulator of tumor progression and angiogenesis. However, little evidence of a correlation between NRP2 expression and lymphangiogenesis has been reported. SEMA3F might suppress lymphangiogenesis by competing with VEGF-C for binding to NRP2.
  
  
  METHODS
  We evaluated lymphatic vessel density (LVD), lymphatic vessel invasion (LVI), the expression levels of VEGF-C, SEMA3F, and NRP2 by immunohistochemistry in 80 cases of oral squamous cell carcinomas (OSCCs).
  
  
  RESULTS
  In these tumors, the expression of NRP2 was positively associated with T stage classification, lymph node metastasis, LVD, LVI, and the expression of VEGF-C. In contrast, low expression of SEMA3F was significantly related to poor differentiation and higher incidence of lymph node metastasis. Patients expressing high levels of VEGF-C or NRP2, or low levels of SEMA3F had a higher risk of recurrence and shorter overall survival. Multivariate analysis showed that VEGF-C and NRP2 were independent prognostic markers for overall survival.
  
  
  CONCLUSIONS
  Results indicate SEMA3F is an inhibitor of tumor progression and provide evidence for an association between NRP2 and VEGF-C, lymphangiogenesis, lymph node metastasis. This suggests the prognostic significance and potential therapeutic value of the VEGF-C/SEMA3F/NRP2 axis for OSCCs.
authors.affiliation: Department of Anatomy, Basic Medical Science College, Harbin Medical University, Harbin, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Harbin Medical University, Harbin, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Zhongxiuzi
authors.initials: Z
authors.lastname: Gao
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Haixia
authors.initials: H
authors.lastname: Li
authors.forename: Haixia
authors.initials: H
authors.lastname: Fan
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zheng
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D039943:Neuropilin-2 / Q000378:metabolism*; D011379:Prognosis; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C491230:SEMA3F protein, human; D042582:Vascular Endothelial Growth Factor C; C581308:neuropilin-2, human
keywords: VEGF-C; lymphangiogenesis; neuropilin-2; oral squamous cell carcinoma; semaphorin 3F