CAJ | 학술논문

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-1 α、ET-1和VEGF的表达.计数资料采用x2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-1α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(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)；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)；进一步分析发现:上述3种检测指标阳性表达率随GIST NIH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-1α、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％(x2=6.325,6.124,6.287,P＜0.05).结论 HIF-1α、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.
목적 탐토결양유도인자-1α(HIF-1α)、혈관내피소-1(ET-1)화혈관내피생장인자(VEGF)재위장도간질류(GIST)중적표체관계급기대환자예후판단적개치.방법 수집2003년1월지2006년12월중남대학상아의원(50례)、호남성소양시중의원(36례)행수술치료적86례GIST환자종류표본,채용면역조직화학염색방법검측표본중HIF-1 α、ET-1화VEGF적표체.계수자료채용x2검험,응용Spearman등급상관분석처리HIF-1α、ET-1화VEGF지간적상관성.Kaplan-Meier법계산환자생존솔,생존분석비교채용Log-rank검험.결과 86례환자중,HIF-1α음성23례、양성30례、강양성33례,양성표체솔위73.3％(63/86)；ET-1음성29례、양성28례、강양성29례,양성표체솔위66.3％ (57/86)；VEGF음성24례、양성26례、강양성36례,양성표체솔위72.1％(62/86).HIF-1α、ET-1화VEGF적표체량량균정정상관(r=0.594,0.655,0.347,P＜0.05)；상술3충검측지표여GIST적미국국립위생연구원(NIH)위험도분급、침윤전이、종류직경화핵분렬상유관(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)；이여환자적성별、년령、종류원발부위무관(x2=0.059、0.071、5.070,0.468、0.074、1.665,0.231、0.370、3.712,P＞0.05)；진일보분석발현:상술3충검측지표양성표체솔수GIST NIH위험도분급적승고、출현침윤전이화종류직경적증대이증가.86례환자수방솔위91.9％(79/86),3、5년생존솔분별위82％화69％.중위수방시간위40.2개월(2～66개월).HIF-1α、ET-1화VEGF양성환자적5년생존솔분별위42％、45％화42％,현저저우음성환자적64％、65％화63％(x2=6.325,6.124,6.287,P＜0.05).결론 HIF-1α、ET-1화VEGF재GIST중적표체량량정정상관,저3충검측지표제시종류적악성정도급환자예후.
Objective To investigate the expression and significance of hypoxia inducible factor-1 α (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-1 α,ET-1 and VEGF in the GIST were detected by immunohistochemical staininng.The relationship between HIF-1 α,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-1α 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-1 α,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,O.071,5.070 ; 0.468,0.074,1.665 ; 0.231,0.370,3.712,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-1 α,ET-1 and VEGF were 42％,45％ and 42％,respectively,and the 5-year survival rates of patients with negative expressions of HIF-1 α,ET-1 and VEGF were 64％,65％ and 63％,respectively.The 5-year survival rates of patients with positive expressions of HIF-1 α,ET-1 and VEGF were significantly lower than those with negative expressions of HIF-1 α,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-1 α,ET-1 and VEGF.HIF-1 α,ET-1 and VEGF could be served as important predictors for the prognosis of patients with GIST.