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非靶标和靶标代谢组学技术在肺癌诊断血清标志物筛选中的应用
郑巍亮1 余江清1▲ 杜芬2 谢宝刚2 贺祥源3
1.江西省景德镇市第一人民医院呼吸内科,江西景德镇 333000;
2.南昌大学药学院,江西南昌 330006;
3.南昌大学第一附属医院胸外科,江西南昌 330006
Application of non-target and target metabolomics techniques in the screening of serum markers for the diagnosis of lung cancer
ZHENG Wei-liang1 YU Jiang-qing1▲ DU Fen2 XIE Bao-gang2 HE Xiang-yuan3
1.Department of Respiratory Medicine,Jingdezheng NO.1 People′s Hospital,Jiangxi Province,Jingdezheng 333000,China; 
2.School of Pharmaceutical Science,Nanchang University,Jiangxi Province,Nanchang 330006,China; 
3.Department of Thoracic Surgery,the First Affiliated Hospital of Nanchang University,Jiangxi Province,Nanchang 330006,China
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摘要 目的 探讨非靶标和靶标代谢组学技术在肺癌诊断血清标志物筛选中的应用价值。方法 2017年7月~2018年12月,通过核磁共振氢谱(1HNMR)代谢组学技术测定47例术后肺癌组织及相邻正常肺组织标本(来自南昌大学第一附属医院及景德镇市第一人民医院),鉴定其代谢产物并找出与肺癌诊断有关的组织差异代谢物;利用超高效液相色谱-串联质谱(UPLC-MS/MS)技术对143例肺癌患者、99例健康对照组血清中胆碱及嘌呤代谢通路上的相关代谢物定量分析;Logistic回归分析和受试者工作特征曲线筛选肺癌诊断的优异代谢物组合。结果 利用1HNMR 的代谢组学分析,脂质、乳酸和甜菜碱为肺癌组织和正常肺组织相关的差异代谢物,推测甲基化相关的代谢物可能与肺癌诊断有关。UPLC-MS/MS 定量分析结果显示:肺癌患者和健康组血清样品中胱硫醚、肉碱、乙酰肉碱、黄嘌呤核苷、鸟苷、鸟嘌呤、肌苷、肌酐、尿苷、胆碱、腺嘌呤、二甲基甘氨酸、腺苷和尿酸等差异有统计学意义(P<0.05);联合胱硫醚、鸟苷、尿酸和腺嘌呤的曲线下面积为0.993,敏感度和特异性均较高(>85%)。结论 非靶标和靶标代谢组学技术测定血清腺嘌呤、鸟苷、尿酸和胱硫醚组合可作为肺癌诊断的潜在血清标志物,值得临床进一步验证和研究。
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郑巍亮
余江清
杜芬
谢宝刚
贺祥源
关键词 肺癌诊断标志物代谢组学核磁共振液质联用    
AbstractObjective To explore the application value of non-target and target metabolomics technology in the screening of serum markers in lung cancer diagnosis.Methods Based on 1HNMR metabolomics,47 cases of post-operative lung cancer tissues and their corresponding normal lung tissue samples from the First Affiliated Hospital of Nanchang University and Jingdezheng NO.1 People′s Hospital were determined to identify their metabolites and obtain the differential metabolites related to the diagnosis of lung cancer from July 2017 to December 2018.The quantitative analysis of related metabolites in serum of 143 lung cancer patients and 99 healthy control group was carried out by ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The excellent metabolite combinations for lung cancer diagnosis were screened based on Logistic regression analysis and receiver operating characteristic curve.Results 1HNMR metabolomics analysis showed that lipids,lactic acid and betaine were differentially metabolites related to lung cancer tissues and normal tissues,suggesting that methylation-related metabolites might be related to the diagnosis of lung cancer.The results of UPLC-MS/MS quantitative analysis showed that the serum samples of lung cancer andhealthy group had significant statistical differences in cystathionine,carnitine,acetyl carnitine,xanthylinucleic acid,guanosine,guanine,inosine,creatinine,uridine,choline,adenine,dimethyl-glycine,adenosine and uric acid (P<0.05).The combined area under the curve of cystathionine,guanosine,uric acid and adenine was 0.993,with high sensitivity and specificity (>85%).Conclusion The combination of non-target and target metabolomics techniques to determine serum adenine,guanosine,uric acid and cystathionine can be used as a potential serum marker for the diagnosis of lung cancer and is worthy of further clinical confirmation and research.
Key wordsDiagnosis of lung cancer;Markers;Metabonomics    HNMR    UPLC-MS/MS
    
基金资助:江西省卫健委科技计划项目(20197249)
作者简介: 郑巍亮(1986-),男,本科,主治医师,研究方向:肺癌早期诊治
引用本文:   
郑巍亮;余江清;杜芬;谢宝刚;贺祥源. 非靶标和靶标代谢组学技术在肺癌诊断血清标志物筛选中的应用[J]. 中国当代医药, 2020, 27(31): 4-8.
ZHENG Wei-liang;YU Jiang-qing;DU Fen;XIE Bao-gang;HE Xiang-yuan3. Application of non-target and target metabolomics techniques in the screening of serum markers for the diagnosis of lung cancer. 中国当代医药, 2020, 27(31): 4-8.
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