HIF-1α和GLUT-1在鼻咽癌组织中的表达及其临床意义

Expression and clinical significance of HIF-1α and GLUT-1 in human nasopharyngeal carcinoma

目的:探究缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)和葡萄糖转运蛋白-1(glucose transporter-1,GLUT-1)在鼻咽癌组织中的表达及其临床意义。方法:选取2010-09至2013-10间经南阳市中心医院确诊为鼻咽癌的79例患者的病理标本及45例慢性鼻咽炎症患者的组织标本,通过免疫组化S-P法测定HIF-1α及GLUT-1蛋白的分布和表达情况;并用CD34进行免疫组化染色定位,计数MVD值;综合分析三者表达的临床意义。通过缺氧诱导剂Co Cl2体外模拟缺氧微环境,初步探讨乏氧条件下HIF-1α对鼻咽癌血管新生的调控机制。结果:免疫组化结果显示HIF-1α蛋白在鼻咽慢性炎症组织中无表达,在鼻咽癌组织细胞核中强阳性表达(阳性率为63.40%),且表达水平和肿块大小、淋巴结转移、T分期和临床分期有关(P<0.05);鼻咽癌组织MVD值明显高于鼻咽慢性炎症组织,且鼻咽癌组织中HIF-1α蛋白的表达与微血管密度呈正相关。GLUT-1在鼻咽慢性炎症组织中呈弱阳性表达(阳性率6.67%),在鼻咽癌组织细胞质(膜)中强阳性表达(阳性率为53.16%),且表达水平和淋巴结转移、临床分期有关(P<0.05);同时鼻咽癌组织中GLUT-1蛋白的表达与MVD呈正相关。另外HIF-1α蛋白与GLUT-1蛋白的表达呈正相关。乏氧条件下鼻咽癌CNE1细胞中HIF-1α、GLUT-1及VEGF蛋白表达均明显升高。结论:HIF-1α和GLUT-1在鼻咽癌组织中高表达,并与鼻咽癌的病理特征和肿瘤血管生成密切相关,其调控血管新生可能是通过激活VEGF来实现的;HIF-1α和GLUT-1似可作为今后诊治鼻咽癌的新靶点。

Objective: To study the expression and clinical significance of HIF-1α and GLUT-1 in human nasopharyngeal carcinoma( NPC). Methods: The expression of HIF-1α and GLUT-1 were examined in tumor tissues collected from79 patients with NPC enrolled into our hospital from September 2010 to October 2013 and in nasopharyngitis tissues from45 patients by using immunohistochemical staining SP method. MVD was counted by immunostaining with anti-CD34 antibody. The expression of HIF-1α,GLUT-1,and VEFG were also determined in CNE1 cells cultured under hypoxia condition. Results: Immunohistochemical staining showed that HIF-1α was highly expressed in nuclei of NPC( positive rate63. 40%) but not in nasopharyngitis tissues. The level of HIF-1α expression was associated with tumor size,lymph metastasis,T stage and clinic stage( P < 0. 05). HIF-1α expression was also positively correlated with MVD,which was significant higher in NPC. GLUT-1 was weakly expressed in nasopharyngitis tissues( positive rate 6. 67%) but strongly expressed in NPC tissues( positive rate 53. 16%). The expression of GLUT-1 in NPC was associated with MVD,lymph metastasis and clinic stage( P < 0. 05). Additionally,hypoxia increased the levels of HIF-1a,GLUT-1 and VEGF in CNE1 cells. Conclusion: The expression of HIF-1α and GLUT-1 are elevated in NPC,which are associated with pathological features and increased MVD. The in vitro study supported the notion that HIF-1α promotes the growth of nasopharyngeal cancer blood vessels through activating VEGF production. These results also suggest that HIF-1a and GLUT-1 are potential targets for the diagnosis and treatment of NPC.