非小细胞肺癌中Keap 1-Nrf 2信号通路蛋白的表达及与临床病理相关性分析

目的 观察胞质蛋白伴侣分子（kelch-like ECH-associated protein-1，Keap1）和核因子E2相关因子（nuclear factor E2 related factors，Nrf2）蛋白在非小细胞肺癌（non-small cell lung cancer，NSCLC）中的表达，探讨两种蛋白与NSCLC的临床联系。方法 采用免疫组化链霉菌抗生物素蛋白-过氧化物酶（streptavidin-perosidase，SP）法和蛋白免疫印迹法检测92例NSCLC组织及其癌旁（≥ 10 cm）中Keapl、Nrf2的蛋白表达，探讨两种蛋白表达与NSCLC肿瘤的组织类型、肿瘤-淋巴结-转移（tumor-node-metastasis，TNM）分期、分化程度、淋巴结转移的相关性。结果 免疫组化染色结果表明，相对于癌旁组织，在NSCLC中Keapl蛋白、Nrf2蛋白表达增加，癌旁组织Keap1、Nrf2蛋白光密度值（optical density，OD）值分别为（0.327±0.053）、（0.313±0.062），而NSCLC组织中两种蛋白OD值明显升高，且NSCLC的分化程度越低，两种蛋白OD值升高越明显；且肿瘤TNM分期越高，Keap1、Nrf2蛋白阳性表达增加；蛋白免疫印迹结果显示，NSCLC组织中Nrf2蛋白、Keapl蛋白表达升高，且与肿瘤组织的分化程度相关。结论 在NSCLC组织中，升高的Nrf2蛋白、Keapl蛋白表达对判断NSCLC的恶性程度有一定的意义。

Expression and clinicopathological correlation of Keap l-Nrf 2 signal pathway protein in non-small cell lung cancer

Objective To observe the expression of kelch-like ECH-associated protein 1 (Keap1) and nuclear factor E2 related factors (Nrf2) protein in non-small cell lung cancer (NSCLC), and to explore its clinical association with NSCLC. Methods Keapl, Nrf2 protein expressions in 92 cases of NSCLC and its adjacent tissues(≥ 10 cm) were detected by immunohistochemical streptavidin-perosidase(SP) method and protein immunoblot method, and their correlation with NSCLC tumor tissue type, tumor-node-metastasis(TNM) stage, the degree of differentiation, lymph node metastasis were analyzed. Results The expression of Keapl protein and Nrf2 protein in NSCLC were increased by immunehistochemical staining. The protein optical density (OD) values of the adjacent tissues were (0.327±0.053) and (0.313±0.062) respectively, and two proteins in the NSCLC tissues were significantly elevated, and the lower the differentiation degree of NSCLC, the more obvious the increase of the two protein OD values. Moreover, the higher of NSCLC tumor T stage, the positive expression of Keap1 and Nrf2 protein increased. The expression of Nrf2 protein and Keapl protein in NSCLC tissues was elevated and correlated with the degree of differentiation of tumor tissues. Conclusions The high expression expression of Nrf2 protein and Keapl protein in NSCLC has some significance in judging the malignancy of tumor.