胃肠道间质瘤PI3K-Akt 信号转导通路促进血管生成相关因子的检测及其意义*

赵 毅; 邓 鑫; 赵 滢; 王 强; 张天彪①

doi:10.3969/j.issn.1000-8179.2010.12.005

胃肠道间质瘤PI3K-Akt 信号转导通路促进血管生成相关因子的检测及其意义*

Detection and significance of the angiogenic factors by PI3K/ AKT signal transduction pathway in gastrointestinal stromal tumors

摘要

摘要: 目的：研究胃肠道间质瘤PI 3K-Akt 信号转导通路促进血管生成相关因子的检测及其意义。方法：Western印迹法检测PI 3K、Akt、PTEN在GIST中的表达，免疫组织化学法检测HIF-1 α 、NOS 2、VEGF在GIST中的表达。结果：在GIST中，随着NIH 分级增高，PI 3K、Akt的蛋白表达水平上调，低危组分别为82.14、115.16；中危组分别为101.34、142.52；高危组分别为138.52、180.55（P<0.05或P<0.01），而抑癌基因PTEN 的蛋白表达水平下调，低危组为114.28；中危组为73.24；高危组为60.12（P<0.05或P<0.01）。 HIF-1 α 、NOS 2 和VEGF的表达与GIST的NIH 分级、黏膜受侵及侵袭转移关系密切（P<0.05或P<0.01）。有侵袭转移组的阳性率明显高于无侵袭转移组。Ⅰ、Ⅱ级与Ⅲ、Ⅳ级患者的HIF-1 α 的阳性率分别为46.2% 、68.4%（P<0.01）；黏膜受侵和无受侵组的患者HIF-1 α 阳性率分别为88.2% 、54.4%（P<0.05）；Ⅰ、Ⅱ级与Ⅲ、Ⅳ级患者NOS 2 的阳性率分别为42.3% 、70.4%（P<0.05）；黏膜受侵和无受侵组的患者NOS 2 阳性率分别为88.2% 、55.7%（P<0.01）；Ⅰ、Ⅱ级与Ⅲ、Ⅳ级患者的VEGF的阳性率分别为46.2% 、61.2%（P<0.01）；黏膜受侵和无受侵组的患者VEGF阳性率分别为79.4% 、50.6%（P<0.01）；HIF-1 α 、NOS 2 和VEGF的的表达未发现与其他临床病理特征有明显的相关性（P>0.05）。 HIF-1 α与NOS 2 蛋白阳性表达之间呈显著正相关（r=0.392，P=0.026）；HIF-1 α与VEGF蛋白阳性表达之间呈显著正相关（r=0.368，P=0.034）；NOS 2 和VEGF蛋白阳性表达之间呈显著正相关（r=0.452，P=0.021）。结论：PI 3K-Akt 信号途径可能通过抑癌基因PTEN的调控来调节HIF-1 α 蛋白的表达，HIF-1 α 、NOS 2 和VEGF以及MVD的表达与GIST的NIH 分级、黏膜受侵及肿瘤侵袭转移关系密切。

Abstract: Objective: To investigate the significance of the angiogenic factors controlled by PI 3K/AKT signaling trans -duction pathway in gastrointestinal stromal tumors. Methods:The expression of PI3K/Akt、PTEN were detected with West-ern-Blot using specimens from 124 cases of GIST . Expression of HIF-1 α, NOS2 and VEGF were detected by immunohisto-chemistry. Results: In gastrointestinal stromal tumors, the protein expression of PI 3K/Akt、PTEN is related to NIH classifica-tion, mucosal invasion and lymphatic metastasis of GIST. The expression of tumor suppressor gene-PTEN is reduced by in -creasing expression of PI 3K and Akt. With the increasing NIH classification the protein expression rates of PI3K and Akt are (82.14;115 .16) in low risk group;( 101 .34;142 .52) in middle risk group and ( 138 .52;180 .55) in hign risk group respective-ly ( P<0.05or P<0.01). The protein expression rate of PTEN is 114 .28in low risk group; 73.24in middle risk group and 60.12 in high risk group ( P<0.05or P<0.01). The protein expression of them has no relationship with age, sex and histological type.The expression of HIF- 1 α 、NOS2 and VEGF is closely related to NIH classification, mucosal invasion and lymphatic metastasis of GIST, too. The positive expression rate of HIF- 1 α is 46.2% 、68.4% (P<0.01) in low risk level and high risk lev-el respectively; and 88.2% 54.4% (P<0.05) in GIST with mucosal invasion and without invasion; The positive expression rate of NOS 2 is 42.3 % 、70.4% (P<0.05) in low risk level and high risk level respectively; and 88.2% 、55.7% (P<0.01) in GIST with mucosal invasion and without invasion; The positive expression rate of VEGF is46.2% 、61.2% (P<0.01)in low risk level and high risk level respectively; and 79.4% 、50.6% (P<0.01) in GIST with mucosal invasion and without invasion;The positive expression rate in metastasis cases is much higher than non-metastaisis cases. The expression of HIF- 1 α 、NOS2 and VEGF has nothing to do with other clinical pathological features. The expression of HIF- 1 α and NOS2 are of sig-nificant positive correlation (r= 0.392 , P=0.026 ). The expression of HIF- 1 α and VEGF are of signi ficant posi tive correlation (r=0.368 , P=0.034 ). The expression of NOS 2 and VEGF are of significant positive correlation (r= 0.452 , P=0.021 ). Conclusion: PI 3K/AKt and PTEN may have control effect on the expression of HIF-1 α. The expression of HIF-1 α 、NOS2,、VEGF and MVD has relationship with the prognosis of GIST.

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