Dynamic relationship between SIPA1 gene and protein expression and the development of gastric cancer

Genet Mol Res. 2017 Mar 16;16(1). doi: 10.4238/gmr16019271.


Association of signal-induced proliferation-associated 1 (SIPA) gene and protein expression with gastric cancer development was examined. SIPA1 mRNA and protein levels were determined by real-time quantitative polymerase chain reaction and western blot, respectively, in 40 gastric tumor and tumor-adjacent normal tissues. SIPA1, VEGF-A, and FVIII levels in 60 gastric tumor and 40 tumor-adjacent normal tissues were examined by immunohistochemical staining. Correlations between SIPA1, VEGF-A, and microvessel density (MVD) were analyzed. SIPA1 mRNA levels were significantly lower in tumor tissues than in tumor-adjacent normal tissues (P < 0.05). Similarly, protein levels were significantly lower in tumor tissues (0.3043 ± 0.1062) than in tumor-adjacent normal tissues (0.5423 ± 0.0682, P < 0.05). Positive staining rates of SIPA1 (48.3%) and VEGF-A (36.7%) were lower and higher, respectively, in tumor tissues than in tumor-adjacent normal tissues (65.0 and 2.5%, P < 0.05). Positive protein staining rates in tumor tissues correlated with the degree of differentiation, lymph node metastases, and clinical grading (P < 0.05) and not with sex, age, or tumor size (P > 0.05). Significantly higher MVD (57.4 ± 9.3) was observed in tumor tissues displaying positive SIPA1 staining than in tumor-adjacent normal tissues (41.2 ± 5.7, P < 0.05). SIPA1 and VEGF-A expression in tumor tissues were negatively correlated (r = -0.736, P < 0.05). SIPA1 and its protein may play important roles in gastric cancer invasion, metastasis, and biological behavior. Low SIPA1 levels in gastric cancer may accelerate tumor development and progression by promoting VEGF-A expression to increase vascular density.

MeSH terms

  • Adult
  • Aged
  • Down-Regulation*
  • Factor VIII / metabolism
  • Female
  • GTPase-Activating Proteins / genetics*
  • GTPase-Activating Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Vascular Endothelial Growth Factor A / metabolism


  • GTPase-Activating Proteins
  • Nuclear Proteins
  • SIPA1 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • F8 protein, human
  • Factor VIII