非小细胞肺癌中GLUT1、HIF-1α的表达及其与FDG摄取的相关性研究

The relationship of expression of GLUT1,HIF-1α and the uptake of FDG in non-small cell lung cancer

背景与目的葡萄糖转运蛋白(GLUT)是介导细胞葡萄糖摄取的主要载体,GLUT1与恶性肿瘤直接相关。在肺癌中GLUT1的表达与肺癌的18F-2-脱氧葡萄糖(FDG)摄取有密切关系,且其表达受乏氧诱导因子-1(HIF-1)的调控。本文拟探讨非小细胞肺癌(NSCLC)中GLUT1、HIF-1α表达与FDG摄取三者之间的相互关系。方法84例NSCLC患者术前行全身PET/CT检查,应用免疫组化方法对肿瘤组织进行GLUT1及HIF-1α检测并记录染色总分,将肺癌组织中GLUT1、HIF-1α的表达水平及FDG标准化摄取值(SUV)进行相关性分析。结果84例NSCLC患者PET/CT检查平均SUV(SUVave)值为3.6～13.2,平均7.8±3.0。SUVave与肿瘤最大直径(Dmax)、TNM分期、病理类型、分化程度均无相关性。84例NSCLC肿瘤标本中GLUT1染色阳性率为95.2%(80/84),染色总分平均值为4.4±1.3。HIF-1α染色阳性率为96.4%(81/84),染色总分平均值为4.4±1.4。GLUT1表达与SUVave值之间呈正相关(r=0.78,P<0.01),HIF-1α表达与SUVave值之间呈正相关(r=0.73,P<0.01),GLUT1表达与HIF-1α表达之间呈正相关(r=0.93,P<0.01)。结论GLUT1、HIF-1α在NSCLC肿瘤组织中均广泛表达,GLUT1在肺癌细胞的葡萄糖摄取及FDG摄取中发挥重要作用,而HIF-1α可能是上调GLUT1表达的重要调控因素之一。

Background and objective It has been known that facilitative glucose transporter(GLUT) is the main carrier which intervenes the glucose uptake of cell,and there is a significant correlation between GLUT1 and cancer.The expression of GLUT1 in lung cancer has close relationship with the uptake of 18fluoro-2-deoxyglucose(FDG) of lung cancer,and the expression of GLUT1 is regulated by hypoxia inducible factor-1(HIF-1).The aim of this study is to investigate the relationship among expression of GLUT1,HIF-1α and the uptake of FDG in non-small cell lung cancer(NSCLC).Methods Eighty-four patients with NSCLC were evaluated with FDG PET/CT before operation.The expression of GLUT1 and HIF-1α was detected immunohistochemically in lung cancer,and their expression level was assessed by the intensity of immunohistochemical staining.Correlation analysis was carried out among the expression level of GLUT1,HIF-1α and the value of standard uptake value(SUV) obtained from preoperative FDG PET/CT examination.Results The range of average SUV(SUVave) of the eighty-four patients was 3.6--13.2,and the average value was 7.8±3.0.There was no significant correlation between the SUVave and the maximum diameter of the tumors,the TNM stage,pathological classification and the degree of differentiation.The positive rate of GLUT1 in the eighty-four patients was 95.2%(80/84).The average intensity of immunohistochemical staining was 4.4±1.3.The positive rate of HIF-1α in the eighty-four patients was 96.4%(81/84).The average intensity of immunohistochemical staining was 4.4±1.4.A highly significant positive correlation was found between GLUT1 expression and the SUVave(r=0.78,P<0.01),and also between HIF-1α expression and the SUVave(r=0.73,P<0.01).There was also a highly significant positive correlation between GLUT1 expression and HIF-1α expression(r=0.93,P<0.01).Conclusion GLUT1 protein and HIF-1α expressions are general in NSCLC tissues.GLUT1 may paly an important role in the glucose and FDG uptake of lung cancer cell,and HIF-1α might be one of the most important regulative factors of GLUT1 expression,which up-regulates the expression of GLUT1.