摘要
目的 5′胞外核苷酸酶(ecto-5′-nucleotidase,CD73)是胞外腺苷生成的关键酶,在多种肿瘤组织中高表达并与肿瘤的发生发展、转移扩散及不良预后有关。CD73在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达与肿瘤微血管密度(microvessel density,MVD)关系尚未完全阐明。本研究应用免疫组化法检测CD73与MVD,分析二者之间的相关性及与临床病理特征的关系和对预后的影响。方法选取山东省医学科学院附属医院2008-06-01-2014-06-01经手术切除的72例NSCLC标本。应用免疫组化法检测CD73在NSCLC组织中的表达,用CD34标记微血管进行MVD计数。结果 CD73阳性表达率为70.8%(51/72),其中弱阳性12.5%(9/72),中等阳性34.7%(25/72),强阳性23.6%(17/72)。CD73表达强度在TNM分期Ⅲ期强于Ⅰ、Ⅱ期(秩均值46.00>31.45),z=-2.931,P=0.003;有淋巴结转移强于无转移(秩均值44.57>30.74),z=-2.884,P=0.004。肿瘤组织中TNM分期Ⅲ期MVD计数为49.72±10.44,Ⅰ、Ⅱ期为31.55±8.75,t=-7.836,P<0.001;肿瘤直径>3cm MVD计数为39.82±12.41,肿瘤直径≤3cm为31.53±12.02,t=-2.423,P=0.018;有淋巴结转移组MVD计数为47.13±10.76,无淋巴结转移组为31.24±9.56,t=-6.600,P<0.001;CD73阳性组MVD计数为41.71±11.592,阴性组为28.52±10.543,t=-4.498,P<0.001。CD73阳性表达与MVD计数呈正相关,r=0.674,P<0.001。通过Kaplan-Meier单因素生存分析发现,CD73阳性组生存率较低,χ2=4.09,P=0.043;多变量Cox回归分析发现,CD73阳性表达(HR=0.378,95%CI:0.172~0.831)是一个不良预后的独立预测指标。结论 CD73在NSCLC中高表达,与不良预后和肿瘤新生血管生成正相关。CD73有望成为一个新的有价值的肿瘤治疗靶点。
OBJECTIVE CD73,known as ecto-5′-nucleotidase,is a pivotal molecule that converts extracellular adenosine monophosphate（AMP）into adenosine.Tumor CD73 expression has been reported in several types of cancer and promotes the onset and progression of tumors,metastatic spread,and determines a poor disease outcome.The clinical signifcance of CD73 expression and MVD in non-small cell lung cancer（NSCLC）,however,has yet to be thoroughly investigated.This study aimed to evaluate CD73 protein expression levels and MVD using immunohistochemistry in 72 resected NSCLC specimens.Associations between their expression profiles and clinicopathological characteristics,as well as patients＇ prognoses,were analyzed.METHODS We collected a total of 72 resected NSCLC tumor specimens from the patients who underwent curative surgical treatment between June 1,2008 and June 1,2014 at Affiliated Hospital of Shandong Academy of Medical Sciences.Immunohistochemistry was used to eval uate the expression of CD73 protein and MVD has been assessed by using CD34 protein.RESULTS Positive CD73 expression was 70.8%（51/72）,including weak12.5%（9/72）,moderate 34.7%（25/72）and strong 23.6%（17/72）.The CD73 expression level was significantly higher in TNM Ⅲ stage than in ⅠⅡ stage（Mean Rank 46.00〉31.45,z=-2.931,P=0.003）,in node-positive than in nodenegative（Mean Rank 44.57〉30.74,z=-2.884,P=0.004）.The MVD value was significantly higher in TNM Ⅲ stage（49.72±10.44）than inⅠⅡstage（31.55±8.75）,t=-7.836,P〈0.001;in tumor size〉3 cm（39.82±12.41）than in tumor size≤3 cm（31.53±12.02）,t=-2.423,P=0.018;in node-positive（47.13±10.76）than in node-negative（31.24±9.56）,t=-6.600,P〈0.001.The value of MVD with CD73 positive expression（41.71±11.592）was significantly higher than with CD73 negative expression（28.52±10.543）,t=-4.498,P〈0.001.The expression level of CD73 was correlated significantly with MVD（r=0.674,P〈0.001）.Kaplan-Meier survival curves were modeled in a univariate analysis：Patients with CD73 positive expression（Log-rank,χ2=4.09,P=0.043）experienced significantly reduced overall survival.Among NSCLC patients,high CD73 expression was an independent indicator of poor prognosis in multivariate Cox regression analyses for overall survival（HR=2.18,95%CI：0.172-0.831）.CONCLUSION In NSCLC patients,the positive expression of CD73 was correlated with poor prognosis and tumor neovascularization,CD73 will become a new and potential target for cancer therapy.
作者
杨修成
李道堂
高玉军
李山成
杨进东
张平
YANG Xiu-cheng;LI Dao-tang;GAO Yu-jun;LI Shan-cheng;YANG Jin-dong;ZHANG Ping(School of Medicine and Life Sciences ,University of J inan- Shandong Academy of Medical Sciences, J inan 250200 , P. R. China;Department of Thoracic Surgery ,Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan 250031 ,P. R. China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2018年第2期99-105,共7页
Chinese Journal of Cancer Prevention and Treatment
