HIF-α、VEGF和DLL4在非小细胞肺癌中的表达及临床意义

Expressions and Clinical Significance of HIF-α,VEGF and DLL4 in Non-small Cell Lung Cancer

目的探讨Delta样配体4(Delta-like ligand 4,DLL4)、低氧诱导因子α(hypoxia inducible factor alpha,HIF-α)和血管内皮生长因子(vascular endothelial growth factor,VEGF)在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及其临床意义。方法选取河北省胸科医院胸外科2012年10月—2015年11月经手术治疗NSCLC患者的手术切除标本72例作为NSCLC组,另选距离原发肿瘤5 cm以上的肺组织标本(经HE染色病理证实无肿瘤浸润)72例作为正常对照组。通过免疫组化染色的方法检测DLL4、HIF-α及VEGF的表达情况,并结合患者的临床病理资料进行分析。结果 NSCLC组DLL4、HIF-α及VEGF阳性表达率显著高于正常对照组(P<0.01);DLL4、HIF-α及VEGF表达与NSCLC肿瘤分化程度、临床分期、淋巴结转移有关(P<0.05),而与患者年龄、性别、病理类型及肿瘤长径无关(P>0.05);DLL4、HIF-α与VEGF表达两两之间均呈显著正相关(r=0.320、0.366、0.335,P<0.01)。结论DLL4、HIF-α及VEGF在NSCLC发生、发展和转移中可能起协同作用,检测DLL4、HIF-α及VEGF的表达对临床判断非小细胞肺癌发生、发展、预后及研发新的靶向治疗药物有一定的价值。

Objective To investigate the expressions and clinical significance of delta-like ligand 4（ DLL4）,Hypoxia inducible factor alpha（ HIF-α） and Vascular endothelial growth factor（ VEGF） in non-small cell lung cancer（ NSCLC）.Methods A total of 72 samples of NSCLC patients undergoing surgery during October 2012 and November2015 were chosen as NSCLC group,and 72 pulmonic tissue samples more than 5 centimeters away from of the primary tumor,which were confirmed with no tumor invasion by hematoxylin and eosin stain（ HE） staining,were chosen as control group.The expressions of DLL4,HIF-α and VEGF were detected using immunohistochemical staining method,and were analyzed,combined with the pathological data.Results The positive expression rates of DLL4,HIF-α and VEGF in NSCLC group were significantly higher than those in control group（ P〈0.01）.The expressions of DLL4,HIF-α and VEGF related to degrees of tumor differentiation,clinical stages and lymph node metastasis（ P〈0.05）,but the expressions were not related to patients＇ age,gender,pathological types and tumor diameter（ P〈0.05）.The expressions of DLL4,HIF-α and VEGF showed significant positive relation between every two（ r = 0.320,0.366,0.335,P〈0.01）.Conclusion DLL4,HIF-α and VEGF may play a collaborative role in incidence,development and metastasis of NSCLC.It has some value for judging incidence,development and prognosis of NSCLC and studying new targeted therapeutic drugs by detecting the expressions of DLL4,HIF-α and VEGF.