血清核转录因子红系2相关因子2表达与非小细胞肺癌分期和增殖基因表达的相关性分析

Correlation analysis of serum nuclear factor-erythroid 2-related factor 2 expression with staging and proliferative gene expression of non-small cell lung cancer

目的探讨血清核转录因子红系2相关因子2(nuclear factor-erythroid 2-related factor 2,Nrf2)表达与非小细胞肺癌(non-small cell lung cancer,NSCLC)分期和增殖基因表达的相关性。方法选取2018年1月至2020年1月宁夏医科大学总医院收治的120例NSCLC患者为研究对象,根据TNM分期将其分为早期组(Ⅰ期,25例)、中期组(Ⅱ~Ⅲ期,69例)和晚期组(Ⅳ期,26例),选取同期健康志愿者120例纳入对照组。比较四组研究对象血清Nrf2、Kelch样环氧氯丙烷相关蛋白-1(Kelch-like epichlorohydrin-associated protein 1,Keap1)表达水平,比较三组NSCLC患者增殖基因[CD59、配对盒基因6(paired box 6,PAX6)、同源异型盒基因B7(homeobox B7,HOXB7)]信使RNA(messenger RNA,mRNA)的相对表达量,采用Pearson相关分析探讨NSCLC患者血清Nrf2表达水平与增殖基因相对mRNA表达量的关系,绘制受试者操作特征曲线(receiver operating characteristic curve,ROC曲线)评价血清Nrf2表达水平评估NSCLC恶性程度的诊断效能。结果四组研究对象血清Nrf2、Keap1表达水平比较差异均有统计学意义(均P<0.05),且血清Nrf2、Keap1表达水平均为晚期组>中期组>早期组>对照组;三组患者肿瘤组织CD59、PAX6、HOXB7 mRNA相对表达量均显著高于癌旁正常组织(均P<0.05),晚期组肿瘤组织CD59、PAX6、HOXB7 mRNA相对表达量均显著高于早期组和中期组(均P<0.05),中期组肿瘤组织CD59、PAX6、HOXB7 mRNA相对表达量均显著高于早期组(均P<0.05);Pearson相关性分析结果显示,血清Nrf2表达水平与CD59、PAX6、HOXB7 mRNA相对表达量均呈显著正相关(R_(CD59)=0.41,R_(PAX6)=0.37,R_(HOXB7)=0.39,均P<0.05);ROC曲线结果显示,血清Nrf2表达水平评估NSCLC恶性程度的曲线下面积为0.89;当选取血清Nrf2表达水平为18.51 ng/L时,灵敏度和特异度分别为94.8%和89.8%。结论Nrf2参与了NSCLC的发生、发展,可有效反映肿瘤状态,预测患者病情严重程度。

Objective To investigate the correlation between the expression of serum nuclear factor-erythroid 2-related factor 2(Nrf2)and staging and proliferative gene expression of non-small cell lung cancer(NSCLC).Method A total of 120 NSCLC patients admitted to General Hospital of Ningxia Medical University from January 2018 to January 2020 were selected as the research subjects.According to TNM stages,they were divided into early group(stageⅠ,25 cases),intermediate group(stageⅡ~Ⅲ,69 cases)and advanced group(stageⅣ,26 cases),and 120 healthy volunteers were included in control group.The expression levels of Nrf2 and Kelchlike epichlorohydrin-associated protein 1(Keap1)in four groups were compared.The relative expression levels of proliferative gene[CD59,paired box 6(PAX6)and Homeobox B7(HOXB7)]messenger RNA(mRNA)in three groups of NSCLC patients were compared.Pearson correlation analysis was used to investigate the relationship between serum Nrf2 expression level and the relative expression of proliferative gene messenger RNA(mRNA)in NSCLC patients.The diagnostic efficacy of serum Nrf2 expression level to evaluate the degree of malignancy of NSCLC was evaluated by drawing receiver operating characteristic curve(ROC curve).Result There were statistically significant differences in serum Nrf2 and Keap1 expression levels among the four groups(all P<0.05),and the expression levels of serum Nrf2 and Keap1 expression were in advanced group>intermediate group>early group>control group.The mRNA expression levels of CD59,PAX6 and HOXB7 in tumor tissues of three groups were significantly higher than those in adjacent normal tissues(all P<0.05),the mRNA relative expression levels of CD59,PAX6 and HOXB7 in advanced group were significantly higher than those in early group and intermediate group(all P<0.05),the mRNA relative expression levels of CD59,PAX6 and HOXB7 in intermediate group were significantly higher than those in early group(all P<0.05).The results of Pearson correlation analysis showed that there were a significant positive corre lation between serum Nrf2 expression level and the mRNA relative expression levels of CD59,PAX6 and HOXB7(R_(CD59)=0.41,R_(PAX6)=0.37,R_(HOXB7)=0.39,all P<0.05).The ROC curve showed that the area under the curve for evaluating the degree of malignancy of NSCLC by serum Nrf2 level was 0.89.When the expression level of Nrf2 was 18.51 ng/L,the sensitivity and specificity were 94.8%and 89.8%,respectively.Conclusion Nrf2 is involved in the occurrence and development of NSCLC and can effectively reflect tumor status and predict the severity of patients'disease.