Study Of Expression And Mechanism Of HIF And Hypoxia Responsetive Genes BNIP3 In Gastric Adenocarcinoma

Objective: To explore the expression and mechanism of the hypoxia inducible factor (HIF) and their downstream responsetive genes BNIP3 in gastric adenocarcinoma.Methods: The first part of the experiment, immunohistochemical streptavidin/peroxidase(SP) was used to examine the expressions of HIF-1α, HIF-2α, BNIP3 and VEGF in Seventy samples of gastric adenocarcinoma . The second part of the experiment, Western blot method was used to detect the expressions of HIF-1α, HIF-2αand BNIP3 in twelve cases of gastric adenocacinoma and normal tissues.Results: 1.The first part of the experiment(1)The positive expression rate of HIF-1α, HIF-2αand VEGF were 61.4 % , 37.1% and 62. 9 % respectively in gastric adenocarcinoma and significantly higher than in normal mucosa (0%) and dysplasia(23.1%,15.4% and 30.8% respectively).But the positive expression rate of BNIP3 (51.4%) in gastric adenocarcinoma was significantly lower than in dysplasia(92.3%).(2)BNIP3 and VEGF expression was positive correlated with HIF-1αexpression.(3)The expression of HIF-2αwas approximate positive correlated with VEGF expression.(4) The expression of HIF-1αand VEGF was significantly correlated with lymph node metastasis and infiltrative depth.(5) BNIP3 expression was also negative correlated with lymph node metastasis. (6)The five-year-survival rate of this group was 23.8%, in which the HIF-1αand VEGF negative groups was much better than that of the positive groups (14. 49% vs 32.47%和12.43%vs33.55%), the BNIP3 positive groups was much better than that of the negative groups (31.92% vs 17.32%). According to the analysis of the Cox model, HIF-1α, BNIP3 and VEGF may become indexes as clinical recovery.2. The second part of the experiment:The expressions of HIF-1α, HIF-2αand BNIP3 were significantly higher than in normal mucosa.Conclusion: The expression of HIF-1αwas significantly associated with BNIP3 and VEGF expression. The mechanism may be that the elevated level of HIF-1αand HIF-2αby hypoxia induced its target gene BNIP3 and VEGF to express in gastric adenocarcinoma. BNIP3 expression relied on HIF-1αexpression and VEGF expression was regulated not only by HIF-1αexpression but also HIF-2αexpression in gastric adenocarcinoma. The expression of HIF-1αand VEGF related with poor biological behavior of gastric adenocarcinoma. They can be taken as useful marker for predicting poor prognosis of gastric adenocarcinoma, and BNIP3 may delay the progression of tumor.