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

Yan Li, Jin-chen Hu, Jieda Cui, B. Hao, Yongfa Hao, Hong Zhang, Juan Chen
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Abstract

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. Key words: Carcinoma, non-small-cell lung; Oxidative stress; Nicotinamide adenine dinucleotide phosphate oxidase 4; Epithelial mesenchymal transformation
非小细胞肺癌中NADPH氧化酶4与上皮间质转化的相关性
目的探讨烟酰胺腺嘌呤二核苷酸氧化酶4 (NOX4)在非小细胞肺癌组织中的表达与上皮间充质转化(EMT)的关系。方法收集2015年至2018年在宁夏医科大学总医院经病理诊断的非小细胞肺癌患者的手术标本及石蜡包埋或纤维支气管镜下的组织标本作为肺癌组(29例),选择相同肺叶切除或肺切除术并入院或纤维支气管镜下肺良性病变组织作为对照组(20例)。采用免疫组化方法分别检测肺癌组和对照组肺组织标本中NOX4、E-cadherin (E-Ca)和Vimentin的表达。分析NOX4表达与肿瘤分期、远处转移及其他肿瘤生物学行为的关系。结果emt相关标记蛋白Vimentin主要在细胞质中表达,肺癌组和对照组肺组织平均光密度分别为(26.42±8.40)和(11.66±8.30)。Vimentin表达高于对照组,差异有统计学意义(t=6.078, P<0.001)。E-Ca表达主要在细胞膜内表达,肺癌组和对照组E-Ca表达的平均光密度分别为(5.15±6.67)和(14.97±7.68)。E-Ca表达低于对照组,差异有统计学意义(t=-4.819, P<0.001)。NOX4的主要表达位点为细胞质和细胞核。肺癌组和对照组肺组织NOX4表达的平均光密度分别为(29.36±11.60)和(11.27±7.36)。肺癌组NOX4表达量显著高于对照组,差异有统计学意义(t=6.160, P<0.001)。肺癌组NOX4蛋白表达与E-Ca表达呈负相关(r=-0.612, P=0.001), NOX4蛋白表达与Vimentin表达呈正相关(r=0.593, P=0.001)。在对照组中,NOX4蛋白表达与E-Ca表达无相关性(r=0.101, P=0.671), NOX4蛋白表达与Vimentin表达无相关性(r=0.109, P=0.649)。结论NSCLC肿瘤组织中高表达NOX4和emt相关标志物Vimentin,低表达E-Ca。NOX4表达与E-Ca表达呈负相关,与Vimentin表达呈正相关。肺癌组织中存在明显的EMT, NOX4可能通过氧化-抗氧化信号通路参与EMT过程。关键词:肺癌,非小细胞肺;氧化应激;烟酰胺腺嘌呤二核苷酸磷酸氧化酶4;上皮间充质转化
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