NOX4的表达与非小细胞肺癌预后的关系

The relationship between NADPH oxidase 4 and the prognosis of non-small cell lung cancer

目的探索烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(NOX4)的表达与非小细胞肺癌预后的关系。方法收集经病理确诊为肺原位癌和不典型增生患者的石蜡包埋标本作为癌前病变组(20例),选取经病理确诊的非小细胞肺癌患者石蜡包埋的手术标本作为肺癌组(40例),以及经病理确诊为肺癌转移性胸腔积液沉渣的石蜡包埋标本作为肺转移癌组(17例),采用免疫组织化学的方法分别检测各组肺组织标本NOX4的表达情况。分析NOX4蛋白的表达与非小细胞肺癌临床参数,即年龄、性别、吸烟史、肿瘤类型、肿瘤分期、分化程度及淋巴结转移的相关性,并分析NOX4蛋白的表达与患者预后生存的关系。结果NOX4主要表达部位为细胞胞浆及胞核,在癌前病变组、肺癌组及肺转移癌组中NOX4表达的平均光密度值分别为10.06±2.32、19.47±4.71和18.44±3.62,3组比较差异具有统计学意义(P<0.05),肺癌组及转移癌组比癌前病变组表达升高(P<0.05),而肺癌组及转移癌组中NOX4表达差异无统计学意义(P>0.05);在非小细胞肺癌组织中,NOX4的表达与肿瘤分化程度密切相关(P<0.05),并且Kaplan-Meier曲线显示高NOX4表达的患者总体生存率明显低于NOX4低表达或阴性的患者(P<0.05),COX生存分析显示NOX4是影响非小细胞肺癌患者预后的独立危险因素。结论非小细胞肺癌肿瘤组织及转移灶内存在NOX4高表达,NOX4的阳性表达与非小细胞肺癌患者预后密切相关,NOX4可能通过氧化-抗氧化的信号途径参与肿瘤侵袭转移的过程,因此NOX4可能是一个良好的预后标志物。

Objective To explore the relationship between the expression of nicotinamide adenine dinucleotide phosphooxidase 4(NOX4)and the prognosis of non-small cell lung cancer.Methods Paraffin-embedded specimens of patients with pathologically who confirmed lung carcinoma in situ and atypical hyperplasia were collected as the precancerous lesion group(n=20).Paraffin-embedded surgical specimens of pathologically confirmed NSCLC patients were selected as the lung cancer group(n=40),and paraffin-embedded specimens of pathologically confirmed lung cancer metastatic pleural sediment(n=17)were selected as the lung metastatic cancer group.The expression of NOX4 in lung tissue samples of each group was detected by immunohistochemical method.Results The main sites of NOX4 expression were the cytoplasm and nucleus of cells.The average optical density of NOX4 expression in the precancerous lesion group,lung cancer group and lung metastatic cancer group were respectively 10.06±2.32,19.47±4.71 and 18.44±3.62.The expression of NOX4 in the lung cancer group and the metastatic lung cancer group was significantly higher than that in the precancerous lesion group(P<0.05),while there was no statistical difference in the expression of NOX4 in the lung cancer group and the metastatic lung cancer group(P>0.05).In NSCLC tissues,NOX4 expression was closely correlated with the degree of tumor differentiation(P<0.05).Moreover,Kaplan-Meier curve showed that the overall survival rate of patients with high NOX4 expression was significantly lower than that of patients with low or negative NOX4 expression(P<0.05).Cox survival analysis showed that NOX4 was an independent risk factor affecting the prognosis of patients with non-small cell lung cancer.Conclusion There is high expression of NOX4 in tumor tissues of NSCLC,and the positive expression of NOX4 is closely related to the prognosis of NSCLC patients.NOX4 may participate in the process of tumor invasion and metastasis through the oxidation-antioxidant signaling pathway,and may be a good prognostic marker.