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Upregulation of hypoxia inducible factor 1α mRNA is associated with elevated vascular endothelial growth factor expression and excessive angiogenesis and predicts a poor prognosis in gastric carcinoma

查看全文 作　　者：Jie [1,2]Ma;Li [3]Zhang;Guo-Qing [2]Ru;Zhong-Sheng [2]Zhao;Wen-Juan [2]Xu 高影响力作者 机构地区：[1]Department of Pathology, Wenzhou Medical College, Wenzhou 325000, Zhejiang Province, China;[2]Department of Pathology, Zhejiang Provincial Hospital, Hangzhou 310014, Zhejiang Province, China;[3]Shaoxing University Medical College, Shaoxing 312000, Zhejiang Province, China高影响力机构 出　　处：《World Journal of Gastroenterology》索引2007年第13卷第11期,共7页高影响力期刊 基　　金：grant from Zhejiang Province Natural Science Foundation, No. M303843 摘　　要：AIM: To investigate the implication of the hypoxia inducible factor HIF-1α mRNA in gastric carcinoma and its relation to the expression of vascular endothelial growth factor (VEGF) protein, tumor angiogenesis invasion/metastasis and the patient's survival. METHODS: In situ hybridization was used to examine expression of HIF-1α mRNA, and immunohistochemical staining was used to examine expression of VEGF protein and CD34 in 118 specimens from patients with gastric carcinoma. RESULTS: The positive rates of HIF-1α mRNA and VEGF protein were 49.15% and 55.92%, respectively. Positive expressions of HIF-1α and VEGF in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis were dramatically stronger than stage T1-T2 cases and those without vessel invasion, lymph node metastasis and distant metastasis. The mean microvascular density (MVD) in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis was significantly higher than stage T1-T2 tumors and those without vessel invasion, lymph node metastasis and distant metastasis. The mean MVD in tumors with positive HIF-1α and VEGF expression was significantly higher than that in tumors with negative HIF-1α and VEGF expression. The expression of HIF- 1α was positively correlated with VEGF protein. There were positive correlations between MVD and expressionof HIF-1α and VEGF. The mean survival time and the 5-year survival rate in cases with positive expression HIF-1α and VEGF and MVD value ≥ 41.5/0.72 mm2 were significantly lower than those with negative expression of HIF-1α and VEGF and MVD value < 41.5/0.72 mm2. CONCLUSION: Overexpression of HIF-1α is found in gastric carcinoma. HIF-1α may induce the angiogenesis in gastric carcinoma by upregulating the transcription of VEGF gene, and take part in tumor invasion and metastasis. They can be used as prognostic markers of gastric cancer in clinical practice. 关 键 词：低氧诱导因子1Α MRNA 增量调节 血管内皮生长因子 基因表达 过量血管发生 胃癌 预后
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