Nrf2和Keap1蛋白在食管鳞状细胞癌中的表达及意义

Expression and significance of Nrf2 and Keap1 protein in esophageal squamous cell carcinoma

目的大量研究表明核因子E2相关因子2(Nrf2)和Kelch样环氧氯丙胺相关蛋白1(Keap1)与肿瘤发生发展相关。本研究旨在检测食管鳞状细胞癌中Nrf2、Keap1蛋白的表达及其与临床病理参数之间的关系,探讨其在食管癌发生、发展中的意义。方法选择2010年7月—2016年11月期间在新疆医科大学第一附属医院经手术治疗的食管癌患者174例,取食管癌组织标本及癌旁组织,使用免疫组织化学法,分别检测其中Nrf2及Keap1蛋白的表达水平并进行统计学分析,所有数据采用SPSS 17.0统计软件进行分析。结果 (1)Nrf2在食管鳞状细胞癌的表达水平显著高于癌旁正常组织(χ~2=21.259,P<0.001),Keap1在食管鳞状细胞癌的表达水平显著低于癌旁正常组织(χ~2=34.863,P<0.001)。(2)新疆不同民族之间Nrf2、Keap1的表达差异有统计学意义(Nrf2:χ~2=12.674,P=0.020;Keap1:χ~2=11.237,P=0.004)。(3)Nrf2的阳性表达与肿瘤淋巴结转移相关(χ~2=5.040,P=0.036),与食管癌组织分化程度也相关(χ~2=10.187,P=0.020)。Keap1阳性表达与肿瘤淋巴结转移相关(χ~2=6.916,P=0.010)和食管癌组织分化程度相关(χ~2=15.432,P<0.001)。(4)食管鳞状细胞癌中Nrf2和Keap1的表达具有相关性(相关系数r=0.219,P=0.031)。结论食管鳞状细胞癌的发生、发展和转移是多因素共同作用的结果,Nrf2、keap1蛋白参与食管鳞状细胞癌发生、发展过程,对临床进一步研究食管癌的预防和临床治疗及判断预后提供一定的新思路。

Objective Lots of researches had shown that nuclear factor erythroid-2 p45-related factor 2(Nrf2) and Kelch-like ECH-associated protein 1(Keap1) were correlated with the formation and development of tumors.This study was designed to detect the expression of Nrf2 and Keap1 protein in esophageal squamous cell carcinoma and explore its relationship with clinicopathological parameters,and to explore their role in the formation and development of esophageal cancer.Methods From July 2010 to November 2016,the cancer and adjacent tissues of 174 cases of esophageal cancer in the First Affiliated Hospital of Xinjiang Medical University were collected to detect the expression level of Nrf2 and Keap1 protein by using immunohistochemistry.The data was analyzed statistically by using SPSS 17.0 statistical software.Results① The expression level of Nrf2 in the cancer tissues of esophageal squamous cell carcinoma was significantly higher than that in adjacent normal tissues(χ^2= 21.259,P < 0.001),but the expression level of Keap1 in the cancer tissues was significantly lower than that in adjacent normal tissues(χ^2= 34.863,P < 0.001).② There was a statistically significant difference in the expression of Nrf2 and Keap1 among the different ethnic groups in Xinjiang(Nrf2:χ^2= 12.674,P = 0.020,Keap1:χ^2= 11.237,P = 0.004).③ The positive expression of Nrf2 was associated with tumor lymph node metastasis(χ^2= 5.040,P = 0.036) and esophageal cancer tissue grading(χ^2= 10.187,P =0.020).The positive expression of Keap1 was associated with tumor lymph node metastasis(χ^2= 6.916,P = 0.010)and esophageal cancer tissue grading(χ^2= 15.432,P < 0.001).④ There was a correlation between the expression of Nrf2 and Keap1 in esophageal squamous cell carcinoma(r = 0.219,P = 0.031).Conclusion In the formation,development and metastasis of esophageal squamous cell carcinoma,multiple factors may be involved,including Nrf2 and Keap1 proteins.This result will provide some new ideas for the further study of the prevention and clinical treatment of esophageal cancer and prognosis.