机构地区:[1]第四军医大学唐都医院胸腔外科,西安710038 [2]清华大学医学院/生物系,北京100084
出 处:《中国肺癌杂志》2009年第9期983-988,共6页Chinese Journal of Lung Cancer
基 金:陕西省科学技术研究发展计划基金(No.2008K09-01)项目资助~~
摘 要:背景与目的NOK是新近发现的属于RPTKs家族成员癌基因,可促进细胞转化、肿瘤发生、侵袭和转移,但NOK蛋白缺乏膜受体结构,通过何种胞膜受体传导信号而被激活及在非小细胞肺癌(NSCLC)中的表达仍不清楚。本研究通过检测NOK和EGFR蛋白在NSCLC中的表达,分析其表达与病理分类、分级和TNM分期关系以及NOK与EGFR表达的相关性,为进一步研究NOK在肿瘤发生发展中的作用机制提供依据。方法采用免疫组化EnVinsion法检测NOK和EGFR在155例NSCLC中的表达,用统计学分析表达差异性和蛋白间的相关性。结果NOK阳性表达主要定位于细胞胞质中,EGFR定位于胞膜和胞质中。NOK、EGFR蛋白在鳞癌、腺癌中高表达,与相应正常组织表达相比差异明显(P<0.001)。鳞癌、腺癌组间相比NOK、EGFR的表达无统计学差异(P=0.099;P=0.23),但NOK、EGFR在鳞癌、腺癌不同病理分级和TNM不同分期中的表达差异明显(P<0.01)。NOK、EGFR在总的NSCLC及其组织分类的鳞癌、腺癌中的表达率和阳性强度存在相关性(P<0.001),相关系数rs分别为0.742、0.722、0.756。结论NOK在NSCLC中高表达,表达的高低与病理分级及TNM分期有关,可能与NSCLC的发生发展有关;NOK与EGFR蛋白在NSCLC及其组织分类中表达存在很好的相关性,NOK信号通路的激活可能与EGFR有关,这为进一步研究NOK在肿瘤发生发展中的作用及其机制提供重要依据。Background and objective NOK (Novel Oncogene with Kinase-domain) is a newly identified receptor protein-tyrosine kinases (RPTKs) subfamily, which possesses strong oncogenic potential including enhancing cell transformation, tumorigenesis, invasion and metastasis. However, NOK protein lacks extracellular domain, and how the NOK is activated by the membrane receptor and the expression of NOK in non small cell lung cancer (NSCLC) are not clear. Our aim of this study was to investigate the expressions of NOK, EGFR proteins in NSCLC. Methods The expression rates of NOK, EGFR proteins in 155 cases with NSCLC was deteced by immunohistochemical stain; The clinical correlations between two proteins were analyzed by statistics. Results The NOK positive expression was mainly located in cytoplasm and EGFR was mainly located in the plasma membrane and cytoplasm. NOK, EGFR proteins were high expressed in NSCLC and there were extremely differences comparing the expression of N OK, EGFR proteins in squamous cell lung cancer, lung adenocarcinoma with those in corresponding normal tissue respectively (P〈0.001); and there were no significant differences between the two kinds of the cancers for their comparison of NOK, EGFR expression (P=0.099; P=0.23); however, there were significant differences for NOK and EGFR expression among histological grades and TNM stages in squamous cell lung cancers, lung adenocarcinoma (P〈0.01). There were correlation between positive and intensity of NOK and EGFR expression in whatever total NSCLC or squamous cell lung cancer or lung adenocarcinoma (P〈0.001), while the correlation coefficients(rs) were 0742, 0.722, 0.756 respectively. Conclusion The NOK proteins are highly expressed in the NSCLC, and the expression rates of NOK proteins are correlated with the cancers' histological grades and TNM stages, which may be concern with tomorgenesis and progression; the positive expression rate and intensity of NOK protein correlate well with the expression of EGFR prote
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