NOX4在结肠癌组织中的表达及与预后的关系

doi:10.11904/j.issn.1002-3070.2020.05.002

实用肿瘤学杂志 ›› 2020, Vol. 34 ›› Issue (5): 391-397.doi: 10.11904/j.issn.1002-3070.2020.05.002

NOX4在结肠癌组织中的表达及与预后的关系

刘恒昌¹, 魏然¹, 李春香², 刘正¹, 陈海鹏¹, 关旭¹, 赵志勋¹, 邹霜梅³, 王锡山¹, 姜争¹

1.国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院结直肠外科;
2.国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院胸外科;
3.国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院病理科

收稿日期:2020-06-08 出版日期:2020-10-28 发布日期:2020-11-02
通讯作者: 姜争,E-mail:jiangzheng@cicams.ac.cn
作者简介:刘恒昌,男,(1990-),硕士,住院医师,从事结直肠癌相关的研究。
基金资助:
中国科学技术部国家重点研究开发计划(编号:2018YFC1315000/2018YFC1315005);中国医学科学院医学与健康科技创新工程项目资助(编号:2019-I2M-2-002;编号:2017-I2M-1-006;编号:2018-I2M-AI-008);白求恩公益基金爱惜康卓越外科基金项目;中国医学科学院中央级公益性科研院所基本科研业务费课题(编号:2018PT32011/2/3);中国癌症基金会北京希望马拉松专项基金(编号:LC2017A07)

Expression of NOX4 in colon cancer and its relationship with prognosis

LIU Hengchang¹, WEI Ran¹, LI Chunxiang², LIU Zheng¹, CHEN Haipeng¹, GUAN Xu¹, ZHAO Zhixun¹, ZOU Shuangmei³, WANG Xishan¹, JIANG Zheng¹

1. Department of Colorectal Surgery,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;
2. Department of Thoracic Surgery,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College;
3. Department of Pathology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College

Received:2020-06-08 Online:2020-10-28 Published:2020-11-02

摘要/Abstract

摘要： 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。

关键词: 结肠肿瘤, NOX4, TCGA, 列线图, 预后

Abstract: 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.

Key words: Colon neoplasm, NOX4, TCGA, Nomogram, Prognosis

中图分类号:

R735.3+5

刘恒昌, 魏然, 李春香, 刘正, 陈海鹏, 关旭, 赵志勋, 邹霜梅, 王锡山, 姜争. NOX4在结肠癌组织中的表达及与预后的关系[J]. 实用肿瘤学杂志, 2020, 34(5): 391-397.

LIU Hengchang, WEI Ran, LI Chunxiang, LIU Zheng, CHEN Haipeng, GUAN Xu, ZHAO Zhixun, ZOU Shuangmei, WANG Xishan, JIANG Zheng. Expression of NOX4 in colon cancer and its relationship with prognosis[J]. Journal of Practical Oncology, 2020, 34(5): 391-397.

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链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2020.05.002

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2020/V34/I5/391

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NOX4在结肠癌组织中的表达及与预后的关系

Expression of NOX4 in colon cancer and its relationship with prognosis

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