title: Decreased expression of SEMA3A is associated with poor prognosis in gastric carcinoma.
abstract: OBJECTIVE
  SEMA3A (semaphorin-3A), is a secreted protein that belongs to the semaphorin family and can function as both a chemoattractive agent or a chemorepulsive agent. SEMA3A has been shown to be a tumor suppressor in various cancers. This study investigated the expression of SEMA3A in gastric cancer and its prognostic value for gastric cancer patients.
  
  
  METHODS
  We examined the expression of SEMA3A in paired cancerous and matched adjacent noncancerous gastric mucosa tissues by real-time quantitative RT-PCR (qRT-PCR) and western blotting. In vitro, we evaluate the effects of SEMA3A on gastric cancer cell proliferation and migration by MTT, transwell and wound-healing assays. Furthermore, we analyzed SEMA3A expression in 128 patients who underwent resection procedures using immunohistochemistry. The relationships between the SEMA3A expression levels, the clinicopathological factors, and patient survival were investigated.
  
  
  RESULTS
  Our results revealed decreased SEMA3A mRNA (P = 0.0037) and protein (P = 0.033) expression in tumor tissue samples compared with matched adjacent non-tumorous tissue samples. Overexpression of SEMA3A inhibits gastric cancer cell proliferation and migration in vitro. Immunohistochemical staining data showed that SEMA3A expression was significantly decreased in 54.68% of gastric cancer cases. In addition, the chi-square test revealed that low SEMA3A expression was significantly correlated with poor differentiation (P = 0.015), Vascular invasion (P = 0.001), depth of invasion (P < 0.001), lymph node metastasis (P = 0.029), distant metastasis (P = 0.002) and advanced TNM stage (P = 0.003). SEMA3A expression was positively correlated with clinical TNM stage, that suggested the more advanced clinical TNM stage corresponding to the lower expression level of SEMA3A (rs = -0.322, P < 0.001) by Spearman rank correlation analysis. Kaplan-Meier survival analysis demonstrated that low expression of SEMA3A was significantly correlated with a poor prognosis for gastric cancer patients (P < 0.001). The multivariate analysis revealed that SEMA3A expression was an independent prognostic factor of the overall survival rate of patients with gastric cancer.
  
  
  CONCLUSIONS
  SEMA3A expression decreased significantly as gastric cancer progressed and metastasized, suggesting that SEMA3A might serve as a candidate tumor suppressor and a potential prognostic biomarker in gastric carcinogenesis.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Nantong University, Nantong University Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Chong
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Nantong University, Nantong University Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Nantong University, Nantong University Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Nantong University, Nantong University Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Nantong University, Nantong University Nantong 226001, Jiangsu, People's Republic of China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhai
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D040121:Semaphorin-3A / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C108639:SEMA3A protein, human; D040121:Semaphorin-3A
keywords: SEMA3A; gastric cancer; prognosis