非小细胞肺癌组织STAT3信号与靶基因VEGF及VEGF-C关系的研究  

Relationship between STAT3 signaling pathway and its target gene VEGF,VEGF-C in patients with non-small cell lung cancer

作　　者：朱鹏冲 孙志钢[2] 肖伟[2] 张楠[3] 王军[4] 王洲 朱良明[2] 

机构地区：[1]兰州大学第一临床医学院,甘肃兰州730000 [2]山东大学附属济南市中心医院胸外科,山东济南250013 [3]山东大学附属济南市中心医院肿瘤科,山东济南250013 [4]山东大学附属济南市中心医院中心实验室,山东济南250013 [5]山东大学附属省立医院胸外科,山东济南250021

出　　处：《中华肿瘤防治杂志》2016年第12期780-785,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：济南市科技计划(201301051)

摘　　要：目的目前,信号转导和转录激活因子3(signal transducers and activators of transcription-3,STAT3)在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中是否通过激活靶基因血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)、血管内皮细胞生长因子C(vascular endothelial growth factor-C,VEGF-C)促进肿瘤的侵袭转移研究报道较少。本研究通过免疫组化技术探讨NSCLC组织中STAT3、p-STAT3与靶基因VEGF、VEGF-C的关系。方法选取2011-09-01-2011-12-31山东大学附属省立医院胸外科施行肺癌手术的72例NSCLC患者的标本,包括72例NSCLC组织及随机选取的20例癌旁正常肺组织。免疫组化技术检测NSCLC组织及癌旁正常肺组织STAT3、p-STAT3、VEGF和VEGF-C的表达情况。结果 VEGF及VEGF-C蛋白在NSCLC组织中的表达均显著高于癌旁正常肺组织,P值分别为0.012和0.011。VEGF的表达与肿瘤大小(pT)、淋巴结转移(pN)及pTNM分期显著相关,P值均<0.05;VEGF-C的表达与淋巴结转移(pN)显著相关,P=0.015。52例有淋巴结转移的肺癌组织中,VEGF、VEGF-C表达阳性例数分别为37例(71.6%)和36例(69.2%),差异有统计学意义,P<0.05;20例无淋巴结转移的肺癌组织中,VEGF、VEGF-C表达阳性例数分别为8例(40.0%)和7例(35.0%),差异有统计学意义,P<0.01。Spearman等级相关分析表明,在NSCLC组织中STAT3表达与p-STAT3表达呈显著正相关,r=0.307,P=0.009。STAT3(r=0.309,P=0.008)、p-STAT3(r=0.381,P=0.001)表达均与VEGF表达呈显著正相关。结论STAT信号通路可能通过调控VEGF、VEGF-C的表达促进NSCLC的发生发展、浸润转移。OBJECTIVE Currently, whether STAT3 signal is activated in NSCLC by the target gene VEGF and VEGF-C to promote tumor invasion and metastasis is reported rarely. This study aimed to investigate the relationship between STAT3 signaling pathway and its target gene VEGF, VEGF-C in patients with non-small cell lung cancer （NSCLC）, and to study the mechanism of STAT3 signaling pathway occurred in NSCLC. METHODS A total of 72 NSCLC patients were enrolled in this study from September 2011 to December 2011. All patients underwent complete tumor resection （lobeetomy or pneumonectomy） with regional lymph node dissection. We obtained 72 NSCLC specimens and 20 normal paracancerous tissues from these patients. The immunehistochemistry was used to detect the expression levels of STAT3, p-STAT3, VEGF, VEGF-C in NSCLC specimens and paracancerous normal tissues. RESULTS The expressions of VEGF and VEGF-C protein in NSCLC tissues were significantly higher than that in normal paracancerous tissues （P=0. 012 ,P=0. 011）. VEGF protein expression was significantly associated with pT, pN and pTNM（P〈0.05, P=0. 028, P〈0.05）. VEGF-C protein expression was significantly associated with pN （P=0. 015）. VEGF, VEGF-C expression of positive cases was 32 （21. 6%）, 36 （69. 2%） in 52 cases with pN of lung cancer; compared with 8 （40.0%）, 6 （30.0%） in 20 cases with no pN of lung cancer, there were significant differences （P〈0.05, P〈0.01）. In the cancerous tissue group, there was a positive correlation between STAT3 expression and p-STAT3 expression （r 0. 302, P= 0. 009）. The expressions of STAT3, p-STAT3 were significant positive correlated with VEGF expression （r=0. 309, P 0. 008）, （r=0. 381, P=0. 001）. CONCLUSION STAT signaling pathway might promote the development, invasion and metastasis of NSCLC by regulating the expression of VEGF and VEGF-C.

关 键 词：非小细胞肺癌 信号转导和转录激活因子3 血管内皮生长因子 淋巴转移 

分 类 号：R734.2[医药卫生—肿瘤]