CRKL在人非小细胞肺癌中的表达及意义

Expression and significance of CRKL in human non-small-cell lung cancer

目的 CRKL(Crk-Like)基因在肺癌细胞系中存在着一定程度的扩增,我们将探讨接合物蛋白CRKL在非小细胞肺癌中的表达情况及与临床病理因素的关系。方法采用免疫组织化学和WB方法,分别检测了131例非小细胞肺癌组织和30例新鲜的非小细胞肺癌标本中CRKL的表达情况。结果 CRKL在正常支气管上皮细胞中呈阴性表达,而在肺癌组织中有44.3%(58/131)的病例存在阳性表达,WB检测发现肺癌中CRKL的表达明显高于对应的癌旁正常肺组织,CRKL蛋白在肺腺癌中的阳性表达为60.34%明显高于鳞癌(P=0.001),其表达与肺癌的低分化、高p-TNM分期(P=0.0035)、高Ki-67(P=0.0062)增殖指数和不良预后明显相关(P=0.0183)。结论 CRKL在肺癌中高表达,并与分化、分期和不良预后相关,提示CrkL蛋白可能在非小细胞肺癌的发生、发展中发挥作用。

Objective CRKL（Crk-Like） is an adaptor protein and has crucial roles in multiple biological processes, including cell proliferation, adhesion and migration. Amplification of CRKL gene was found in non-small cell lung cancer （NSCLC）, however, the expression pattern of CRKL protein and its clinical significance in human NSCLC have not been well characterized to date. Methods In this study, the expression of CRKL was evaluated in 131 cases of NSCLC tissues by immumohistochemistry and WB methods, and its clinical significance was analyzed. Results CRKL protein was up-regulated in the lung carcinomas compared with adjacent normal lung tissue. Overexpression of CRKL was found in 58 of 131 cases（44.3%） of NSCLC samples and correlated with poor tumor differentiation （P=0.0042）, histological type （adenocarcinoma, P=0.001）, advanced p-TNM stage （P =0.0004）, lymph nodal metastasis （P=0.0273）, high proliferation index （P=0.0062） and poor overall survival （P=0.0084）. Further univariate and multivariate analysis showed a significant association of CRKL overexpression and worse overall survival in lung cancer patients. Conclusion The overexpression of CRKL correlated with poor prognosis and lung cancer proliferation by cell cycle regulation in NSCLC.