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缺氧诱导因子-α和血管内皮素-1及血管内皮生长因子在胃肠道间质瘤中的表达及意义 被引量:8

Expression and significance of hypoxia inducible factor-la and endothelin-I and vascular endothelialgrowth factor in gastrointestinal stromal tumor
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摘要 目的探讨缺氧诱导因子-1α(HIF-1α)、血管内皮素-1(ET-1)和血管内皮生长因子(VEGF)在胃肠道间质瘤(GIST)中的表达关系及其对患者预后判断的价值。方法收集2003年1月至2006年12月中南大学湘雅医院(50例)、湖南省邵阳市中医院(36例)行手术治疗的86例GIST患者肿瘤标本,采用免疫组织化学染色方法检测标本中HIF-1α、ET-1和VEGF的表达。计数资料采用r检验,应用Spearman等级相关分析处理HIF-1α、ET-1和VEGF之间的相关性。Kaplan—Meier法计算患者生存率,生存分析比较采用Log—rank检验。结果86例患者中,HIF-1仅阴性23例、阳性30例、强阳性33例,阳性表达率为73.3%(63/86);ET-1阴性29例、阳性28例、强阳性29例,阳性表达率为66.3%(57/86);VEGF阴性24例、阳性26例、强阳性36例,阳性表达率为72.1%(62/86)。HIF-1α、ET-1和VEGF的表达两两均呈正相关(r=0.594,0.655,0.347,P〈0.05);上述3种检测指标与GIST的美国国立卫生研究院(NIH)危险度分级、浸润转移、肿瘤直径和核分裂象有关(,=15.565、10.841、12.574、21.125,8.171、10.002、10.354、17.317,14.710、16.230、11.116、18.886,P〈0.05);而与患者的性别、年龄、肿瘤原发部位无关(X2=0.059、0.071、5.070,0.468、0.074、1.665,0.231、0.370、3.712,P〉0.05);进-步分析发现:上述3种检测指标阳性表达率随GISTNIH危险度分级的升高、出现浸润转移和肿瘤直径的增大而增加。86例患者随访率为91.9%(79/86),3、5年生存率分别为82%和69%。中位随访时间为40.2个月(2—66个月)。HIF-1仪、ET.1和VEGF阳性患者的5年生存率分别为42%、45%和42%,显著低于阴性患者的64%、65%和63%(,=6.325,6.124,6.287,P〈0.05)。结论HIF-1d、ET-1和VEGF在GIST中的表达两两呈正相关,这3种检测指标提示肿瘤的恶性程度及患者预后。 Objective To investigate the expression and significance of hypoxia inducible factor-1α ( HIF-1α), endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) in gastrointestinal stromal tumor (GIST). Methods Eighty-six samples of GIST specimens were collected from Xiangya Hospital (50 cases) and Shaoyang Chinese Medicine Hospital (36 cases) from January 2003 to December 2006. The expressions of HIF-1α, ET- 1 and VEGF in the GIST were detected by immunohistochemieal staininng. The relationship between HIF-1α, ET-1 and VEGF was analyzed by using the Spearman rank correlation. The survival rates were calculated by using the Kaplan-Meier method, and the survival was analyzed using the Log-rank test. The count data were analyzed using the chi-square test. Results The expression of HIF-1 ct was negative in 23 cases, positive in 30 cases, strongly positive in 33 cases, and the overall positive rate was 73.3% (63/86) ; the expression of ET-1 was negative in 29 cases, positive in 28 cases and strongly positive in 29 cases, and the overall positive rate was 66.3% (57/86) ;the expression of VEGF was negative in 24 cases, positive in 26 cases, strongly positive in 36 cases, and the overall positive rate was 72.1% (62/86). There was a positive corelation between the expressions of HIF-1α, ET-1 and VEGF (r =0. 594, 0.655, 0. 347, P 〈 0.05). The positive expressions of HIF-1α, ET-1 and VEGF were correlated with National Institute of Health (NIH) risk stratification, infiltration and metastasis, tumor diameter and number of nuclear division of GIST (X2= 15. 565, 10. 841, 12. 574, 21. 125; 8. 171, 10. 002, 10. 354, 17. 317; 14. 710, 16. 230, 11. 116, 18. 886, P〈0.05), but not with the gender, age and the initial occurring position of the tumor (X2= 0. 059, 0. 071, 5. 070 ; 0. 468, 0. 074, 1. 665 ; O. 231,0. 370, 3. 712, P 〉 0.05). The positive expression rates of HIF-1α, ET-1 and VEGF increased as the increase of the malignant level of GIST, tumor infiltration and metastasis and the tumor diameter. The follow up rate was 91.9% (79/86), and the 3- and 5-year survival rates were 82% and 69%, respectively. The median survival rate was 40.2 months (range, 2-66 months). The 5-year survival rates of patients with positive expressions of HIF-1α, ET-1 and VEGF were 42%, 45% and 42%, respectively, and the 5-year survival rates of patients with negative expressions of HIF-1α, ET-1 and VEGF were 64% , 65% and 63%, respectively. The 5-year survival rates of patients with positive expressions of HIF-1α, ET-1 and VEGF were significantly lower than those with negative expressions of HIF-1α, ET-1 and VEGF (X2 = 6. 325, 6. 124, 6. 287, P 〈 0.05). Conclusion There is a positive correlation between the expressions of HIF-1α, ET- 1 and VEGF. HIF- 1 oL, ET- 1 and VEGF could be served as important predictors for the prognosis of patients with GIST.
出处 《中华消化外科杂志》 CAS CSCD 北大核心 2013年第4期290-293,共4页 Chinese Journal of Digestive Surgery
基金 湖南省卫生厅基金(B2008-091)
关键词 胃肠道间质肿瘤 缺氧诱导因子 血管内皮素-1 血管内皮生长因子 免疫组织化 学染色 Gastrointestinal stromal tumor Hypoxia inducible factor Endothelin-l Vascularendothelial growth factor Imunohistoehemiscal staining
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