缺氧诱导因子及其应答基因BNIP3和血管内皮生长因子在胃腺癌中表达及临床意义

目的检测缺氧诱导因子（HIF）及其应答基因bcl-2／腺病毒E1B19000相互作用蛋白3（BNIP3）和血管内皮生长因子（VEGF）在胃腺癌中的表达，探讨它们之间的关系以及在胃腺癌中表达的临床意义。方法采用免疫组化S-P法，检测70例胃腺癌组织和12例癌旁正常组织中HIF-1α、HIF-2α、BNIP3和VEGF的表达。结果70例胃腺癌组织中，HIF—1α、HIF-2α、BNIP3和VEGF的阳性表达率分别为61．4％、37．1％、51．4％和62．9％；而在正常对照组中的阳性表达率分别为8．3％、0、0和0，4种基因在不同组织间的表达率差异均有统计学意义（P〈0．01）。HIF—1α和VEGF的表达与胃腺癌淋巴结转移密切相关，BNIP3的表达与淋巴结转移呈负相关；HIF-1α的表达与BNIP3和VEGF的表达呈正相关。结论HIF通过调节其下游基因的表达在胃癌的发生和发展中发挥着重要作用；VEGF的表达与胃腺癌的不良生物学行为相关，而BNIP3的表达则提示预后较好。

Expression and function of HIF and its target genes BNIP3, VEGF in gastric adenocarcinoma

Objective To explore the expression and mechanism of the hypoxia inducible factor (HIF) and their downstream responsive genes BNIP3, VEGF in gastric adenocarcinoma, and to investigate their clinical significance. Methods SP immunohistochemical method was used to detect the expression of HIF-1α, HIF-2α, BNIP 3 and VEGF in the tissue samples from 70 gastric adenocarcinoma patients. Results Compared with the normal tissue, gastric adenocarcinoma had significantly higher positive expression rate of HIF-1α(61.4% vs. 8.3%), HIF-2α(37.1% vs.0), BNIP3(51.4% vs.0) and VEGF(62.9% vs. 0). The expression of BNIP3 and VEGF was positively correlated with HIF-1α expression. The expressions of HIF-1α and VEGF was significantly and positively correlated with lymph node metastasis, while BNIP3 expression was negatively correlated with that. Conclusion Accumulation of hypoxia inducible factors regulate the expression and function of its downstream target genes, which may play a critical role in the carcinogenesis of gastric adenocarcinoma. VEGF expression is found to be related to poor biological behavior, but BNIP3 expression may suggest better prognosis of gastric adenocarcinoma.