NOX4在结肠癌组织中的表达及与预后的关系

目的 观察结肠癌组织中NADPH氧化酶-4(NOX4)的表达情况,并探讨其与结肠癌预后的关系。方法 选择我院2015年1月—12月期间就诊的80例结肠癌患者石蜡标本,进行免疫组化染色,在癌症和肿瘤基因图谱(TCGA)数据库中获取结肠癌COAD数据集,观察NOX4在结肠癌组织中的表达情况以及对预后的判断价值。应用生物信息学方法,分析与NOX4相关的基因和信号通路。构建预测结肠癌患者预后的列线图,应用C指数评价列线图的预测效能。根据预后风险评分将患者分为高风险组和低风险组,应用Kaplan-Meier法比较两组患者预后情况。结果 NOX4在结肠癌组织中的表达显著高于正常肠粘膜组织,表达水平随着分期的升高而增加;NOX4高表达的患者的预后较低表达患者的预后更差(P＜0.05);基因富集分析结果显示NOX4可能参与JAK-STAT、MAPK、TGFβ和WNT等肿瘤相关信号通路的调控,白介素-1和白介素-6的产生以及分泌;Cox多因素回归分析结果提示年龄、N分期、M分期、术后化疗以及NOX4的表达是影响结肠癌患者总生存期(OS)的独立危险因素;应用这些因素建立预测结肠癌患者OS的列线图,C指数分别为0.735(内部验证)和0.727(外部验证);校正曲线表明该列线图具有较好的预测效能。结论 NOX4在结肠癌组织中的表达显著升高,是影响结肠癌患者预后的独立危险因素;构建的基于NOX4的预后模型具有较好的预测效能。

Expression of NOX4 in colon cancer and its relationship with prognosis

Objective The Objective of this study was to investigate the expression of NADPH oxidase-4(NOX4)in colon cancer and to explore its relationship with the prognosis of colon cancer.Methods Eighty paraffin specimens of colon cancer patients treated in our hospital from January to December 2015 were selected for immunohistochemical staining.The COAD data set of colon cancer was obtained from the Cancer and Tumor Gene Atlas(TCGA)database to observe the expression of NOX4 in colon cancer and its prognostic value.Bioinformatics methods were used to analyze the genes and signal pathways related to NOX4.A nomogram was constructed to predict the prognosis of colon cancer patients,and the C index was used to evaluate the prediction effect of nomogram.According to the prognosis risk score,patients were divided into the high-risk group and the low-risk group,and the Kaplan-Meier method was used to compare the prognosis of the two groups.Results The expression of NOX4 in colon cancer tissues was significantly higher than that in normal intestinal mucosa tissues,and its expression level increased with the increase of cancer stage.The prognosis of patients with high expression of NOX4 was worse than those with low expression(P＜0.05).The results of gene enrichment analysis showed that NOX4 might be involved in the regulation of tumor-related signal pathways such as JAK-STAT,MAPK,TGF-β and WNT,and the production and secretion of interleukin-1 and interleukin-6.The results of Cox multivariate regression analysis showed that age,N stage,M stage,postoperative chemotherapy and the expression of NOX4 were independent risk factors affecting OS in colon cancer patients.These factors were used to establish a nomogram for predicting OS in patients with colon cancer,the C index was 0.735(internal validation)and 0.727(external validation).The calibration curve showed that the nomogram had better predictive performance.Conclusion The expression of NOX4 in colon cancer tissues is significantly increased,and it is an independent risk factor affecting the prognosis of colon cancer patients.The constructed prognosis model based on NOX4 has a good predictive power.