Expression Of KIF3A In Gastric Adenocarcinoma And Its Effect On Metastasis In Vitro

Objective To explore the expression of KIF3 A protein in different gastric lesions,and to analyze its relationship to clinicopathological features and survival time of patients with advanced gastric adenocarcinoma;To investigate the effect of KIF3 A on the migration,invasion and proliferation of gastric adenocarcinoma cells in vitro,and to explore the significance of KIF3 A on the tumorigenesis,development and prognosis of gastric adenocarcinoma.Methods The expression of KIF3 A was detected immunohistochemically in 118 pairs gastric adenocarcinoma and corresponding adjacent non-tumor tissue,39 cases corresponding metastatic lymph nodes of gastric adenocarcinoma,12 cases low grade intraepithelial neoplasia and 12 cases high grade intraepithelial neoplasia,and the relationship was analyzed between KIF3 A expression and the tumorigenesis,clinicopathological characters,prognosis of advanced gastric adenocarcinoma.The western blot was performed to examine the expression of KIF3 A in 16 pairs of fresh gastric adenocarcinoma and corresponding adjacent non-tumor tissue,and the difference of expression was compared.The lentiviral vector HBLV-h-sh KIF3 A was constructed,and the expression of KIF3 A in gastric adenocarcinoma cells SGC-7901,BGC-823 and MGC-803 was silenced.The effect of KIF3 A on morphology of gastric adenocarcinoma cells was examined by optical microscope.Wound healing assay and Transwell assay were applied to detected the migratory and invasive capability of gastric adenocarcinoma cells.The proliferation of SGC-7901,MGC-803 and BGC-823 cell lines was examined by colony formation assay and MTT assay.Western blot was also performed to examine the expression of E-cadherin,vimentin,MMP2,MMP9 and PCNA.Results The KIF3 A protein expression was upregulated in 16 pairs fresh gastric adenocarcinoma by western blot(P<0.05).The high-expression rate of KIF3 A protein was very high in gastric adenocarcinoma(51/118)than that in corresponding adjacent non-tumor tissue(24/118)(P<0.01).The expression of KIF3 A was very lower in chronic gastritis than that both in low-grade and high-grade intraepithelial neoplasia tissue(P<0.01).The KIF3 A was obvious higher-expressed in lymph node secondary tumor than that in corresponding primary tumor(P<0.01).KIF3 A high-expression rate was associated with lymph node metastasis,TNM stage and vascular invasion of advanced gastric adenocarcinoma(P<0.05).Survival analysis showed that patients with KIF3 A low-expression had better prognosis than those with KIF3 A high-expression(P<0.01).In the group of lymph node metastasis,the overall survival time of patients with KIF3 A high-expression was shorter than those with KIF3 A low-expression(P<0.05).In the group of TNM stage III and IV,the overall survival time of patients with KIF3 A high-expression was significant shorter compared to those with KIF3 A low-expression(P<0.01).In the group of KIF3 A expression,the overall survival time of patients with KIF3A-positive in nucleus was lower compared to those with KIF3A-negative in nucleus(P<0.05).Cox regression model analysis revealed that KIF3 A was an independent prognostic factor for overall survival and disease-free survival of patients with advanced gastric adenocarcinoma.The results of Transwell assay and wound healing assay showed that silencing KIF3 A in gastric adenocarcinoma cells inhibited cells migration and invasion(P<0.05).MTT assay and colony formation assay results revealed that silencing KIF3 A in gastric adenocarcinoma cells inhibited proliferation ability of cells(P<0.05).And silencing KIF3 A in gastric adenocarcinoma cells decreased expression of MMP2,MMP9 and PCNA(P<0.05),but was no obviously effect on expressing of E-cadherin,vimentin(P>0.05),and morphology of gastric adenocarcinoma cells.Conclusion KIF3 A may relate to the tumorigenesis of gastric adenocarcinoma,and may promote the invasion and metastasis of gastric adenocarcinoma.It may be served as a new potential marker for estimating the prognosis of patients with gastric adenocarcinoma.Silencing KIF3 A in gastric adenocarcinoma cells can inhibit cell migration,invasion and proliferation in vitro.It may affect the cell migration and invasion by regulating the expression of MMP9 and MMP2,but may be no notable effects on epithelial-mesenchymal transformation in cell lines.The detailed mechanism of KIF3 A can promote cell proliferation needs to be further studied in the future.