NADPH氧化酶4与非小细胞肺癌上皮间质转化的相关性研究

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上皮间质转化(EMT)的关系。方法收集2015~2018年在宁夏医科大学总医院经病理确诊的非小细胞肺癌患者石蜡包埋的手术标本和或纤维支气管镜取材组织标本作为肺癌组(29例),选取同期入院行肺叶或肺段切除和或纤维支气管镜取材的肺良性病变组织作为对照组(20例),采用免疫组织化学方法分别检测肺癌组及对照组肺组织标本NOX4、E-钙粘连蛋白(E-Ca)及波形蛋白(Vimentin)的表达情况。分析NOX4表达与肿瘤分期、远隔转移等肿瘤生物学行为间的相互关系。结果EMT相关标志蛋白Vimentin主要表达部位在细胞浆,在肺癌组及对照组肺组织表达的平均光密度值分别为(26.42±8.40)和(11.66±8.30),Vimentin表达高于对照组,且差异具有统计学意义(t=6.078,P<0.001);E-Ca主要表达部位在细胞膜,肺癌组及对照组E-Ca表达的平均光密度值分别为(5.15±6.67)和(14.97±7.68),E-Ca表达低于对照组,差异具有统计学意义(t=-4.819,P<0.001)。NOX4主要表达部位为细胞胞浆及胞核,NOX4在肺癌组及对照组肺组织表达的平均光密度值分别为(29.36±11.60)和(11.27±7.36),肺癌组表达较对照组明显增高,差异有统计学意义(t=6.160,P<0.001)。肺癌组NOX4蛋白的表达与E-Ca的表达呈负相关性(r=-0.612,P=0.001),NOX4的表达与Vimentin的表达呈正相关性(r=0.593,P=0.001);在对照组,NOX4蛋白的表达与E-Ca的表达无相关性(r=0.101,P=0.671),NOX4与Vimentin的表达无相关性(r=0.109,P=0.649)。结论非小细胞肺癌肿瘤组织存在NOX4以及EMT相关标志物Vimentin高表达,E-Ca低表达。NOX4表达与E-Ca表达呈负相关性,与Vimentin表达呈正相关性。肺癌组织内存在明显的EMT,NOX4可能通过氧化-抗氧化的信号途径参与EMT的过程。

Correlation between NADPH oxidase 4 and epithelial mesenchymal transformation in non-small cell lung cancer

Objective To explore the relationship between the expression of nicotinamide adenine dinucleotide oxidase 4(NOX4)and epithelial mesenchymal transformation(EMT)in non-small cell lung cancer.Methods Collected from 2015 to 2018 in ningxia medical university general hospital by pathological diagnosis of non-small cell lung cancer patients with surgical specimens and paraffin embedding or fiber bronchoscope based tissue samples as lung cancer group(29 cases),select the same lobectomy or lung resection and admission or fiber bronchoscope lung benign lesions of organization as the control group(20 cases),immunohistochemical method is used respectively to detect lung cancer groups and control group in the lung tissue specimens NOX4,E-cadherin(E-Ca)and Vimentin expression.To analyze the relationship between NOX4 expression,tumor staging,distant metastasis and other tumor biological behaviors.Results The EMT-related marker protein Vimentin was mainly expressed in the cytoplasm,and the average optical density of the lung tissue in the lung cancer group and the control group was(26.42±8.40)and(11.66±8.30),respectively.The expression of Vimentin was higher than that in the control group,and the difference was statistically significant(t=6.078,P<0.001).E-Ca expression was mainly expressed in the cell membrane,and the average optical density of E-Ca expression in the lung cancer group and the control group was(5.15±6.67)and(14.97±7.68),respectively.E-Ca expression was lower than that in the control group,and the difference was statistically significant(t=-4.819,P<0.001).The main expression sites of NOX4 were cytoplasm and nucleus of cells.The average optical density of NOX4 expression in lung tissues of lung cancer group and control group was(29.36±11.60)and(11.27±7.36),respectively.The expression of NOX4 in lung cancer group was significantly higher than that in control group,and the difference was statistically significant(t=6.160,P<0.001).NOX4 protein expression in lung cancer group was negatively correlated with E-Ca expression(r=-0.612,P=0.001),and NOX4 expression was positively correlated with Vimentin expression(r=0.593,P=0.001).In the control group,NOX4 protein expression was not correlated with E-Ca expression(r=0.101,P=0.671),and NOX4 protein expression was not correlated with Vimentin expression(r=0.109,P=0.649).Conclusions High expression of NOX4 and EMT-related markers Vimentin and low expression of E-Ca were found in tumor tissues of NSCLC.NOX4 expression was negatively correlated with E-Ca expression,and positively with Vimentin expression.There is obvious EMT in lung cancer tissues,and NOX4 may participate in the EMT process through the oxidation-antioxidant signaling pathway.