Delta样配体4和血管内皮生长因子在非小细胞肺癌中的表达及临床意义
The expressions of Delta-like ligand 4 and vascular endothelial growth factor in non-small cell lung cancer and their clinical significances
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摘要: 目的:检测Delta样配体4(DLL4)和血管内皮生长因子(VEGF)在非小细胞肺癌(NSCLC)及癌旁正常组织中的表达,分析其与NSCLC临床病理参数的关系及两者表达的相关性,探讨它们在NSCLC发生发展中的作用。方法:应用免疫组织化学EliVision法检测73例NSCLC组织标本中DLL4和VEGF表达,以32例NSCLC癌旁正常组织作对照。结果:DLL4、VEGF在NSCLC组织中的表达均明显高于癌旁正常组织中的表达(P0.01);在NSCLC组织中,不同TNM分期、淋巴结转移(DLL4除外)和分化程度,DLL4、VEGF的阳性表达差异均有统计学意义(P0.05～P0.01),而在性别、年龄和组织学类型间其阳性表达差异均无统计学意义(P0.05);DLL4和VEGF在NSCLC组织表达呈正相关关系(P0.05)。结论:DLL4、VEGF高表达可能相互作用,共同促进NSCLC的浸润转移,从而影响患者预后,DLL4、VEGF可能为NSCLC的靶向治疗提供新方法。Abstract: Objective:To investigate the expressions of Delta-like ligand 4(DLL4) and vascular endothelial growth factor(VEGF) in non-small cell lung cancer(NSCLC) and normal lung specimens taken from non-cancerous regions adjacent to lung cancer tissue and analyze their correlation with clinical pathological factors as well as explore the role of them in the occurrence and development of NSCLC.Methods:The expressions of DLL4 and VEGF in 73 cases of NSCLC tissue and 32 cases of normal lung specimens taken from non-cancerous regions adjacent to lung cancer tissue were examined by EliVision immunohistochemistry method.Results:The positive rate of DLL4 and VEGF in NSCLC were significantly higher than those in adjacent normal lung tissue.In NSCLC tissues,the expressions of DLL4 and VEGF were closely related to TNM stage,lymph node metastasis(except DLL4) and histological grade(P0.05 to P0.01),but not to gender,age and histological type(P0.05).A positive correlation was observed between the expressions of DLL4 and VEGF(P0.05).Conclusions:The positive correlation between high-expressions of DLL4 and VEGF suggested that they might co-participate in the invasion/metastasis and prognosis of NSCLC through interacting with each other.DLL4 and VEGF may serve as a new therapeutic target of NSCLC patients.
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[2] Gao J,Song Z,Chen Y,et al.Deregulated expression of Notch receptors in human hepatocellular carcinoma[J].Dig Liver Dis,2008,40( 2):114-121. [2] 王彩琴,郑惠珍.Delta 样配体4 /Notch 信号通路与血管新生的研究进展[J].广东医学院学报,2010,28( 6):687-688. [3] Jubb AM,Turley H,Moeller HC,et al.Expression of delta-like ligand 4( Dll4) and Markers of hypoxia in colon cancer[J].Br J Cancer, 2009,101( 10):1749-1757. [4] Jubb AM,Soilleux EJ,Turley H,et al.Expression of vascular notch ligand delta-like 4 and inflammatory markers in breastcancer[J].Am J Pathol,2010, 176( 4):2019-2028. [5] Patel NS,Li JL,Generali D,et al.Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function[J].Cancer Res,2005,65( 19):8690-8697. [6] Li JL,Sainson RC,Shi W,et al.Delta-like 4 Notch ligand regulates tumor angiogenesis, improves tumor vascular function,and promotes tumor growth in vivo[J].Cancer Res,2007,67( 23):11244-11253. [7] Yoon HA,Noh MH,Kim BG,et al.Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma [J].World J Gastroenterol, 2011,17( 35):4023-4030. [8] Hainaud P,Contreres JO,Villemain A,et al.The role of the vascular endothelial growth factor-Delta-like 4 ligand /Notch4-ephrin B2 cascade in tumor vessel remodeling and endothelial cell functions[J].Cancer Res,2006, 66( 17):8501-8510. [9] Semenza GL.O2 -regulated gene expression:transcriptional control of cardiorespiratory physiology by HIF-1[J].J Appl Physiol,2004,96( 3):1173-1177. [10] Farkkila A,Anttonen M,Pociuviene J, et al.Vascular endothelial growth factor ( VEGF ) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors[J].Eur J Endocrinol,2011,164( 1):115-122. [11] Hirakawa S,Kodama S,Kunstfeld R,et al.VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis [J].J Exp Med,2005,201 ( 7 ):1089-1099. [12] Ridgway J,Zhang G,Wu Y,et al.Inhibition of Dll4 signalling inhibits tumor growth by deregulating angiogenesis[J].Nature,2006, 444( 7122):1083-1087. [13] Liu ZJ,Shirakawa T,Li Y, et al.Regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells:implications for modulating arteriogenesis and angiogenesis[J].Mol Cell Biol,2003,23( 1):14-25. [14] Sandler A,Gray R,Perry MC, et al.Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer[J].N Engl J Med,2006, 355( 24):2542-2550. -
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