【作者】 郭巍；

【导师】 王凯臣；

【作者基本信息】 吉林大学 ， 临床医学硕士（专业学位）， 2023， 硕士

【摘要】 目的:定量检测非肌层浸润性膀胱癌(Non-muscle-invasive bladder cancer,NMIBC)患者与健康对照组尿液样本内源性大麻素含量,验证内源性大麻素类物质花生四烯酸乙醇胺(arachidonoylethanolamine,AEA)、硬脂酰胺(stearoylethanoamide,SEA)作为NMIBC早期非侵入性诊断标志物的可行性,明确诊断性能。方法:收集2021年9月至2022年11月在吉林大学白求恩第三临床医院入院治疗的21例首次被诊断NMIBC患者术前尿液样本及12例健康对照组尿液样本,所有患者均无其他恶性肿瘤病史、放化疗史及其它泌尿系统良性疾病。将患者尿液样本离心,使用梯度洗脱对待测物进行分离;使用电喷雾离子源(Electron Spray Ionization,ESI)对待测物进行离子化,利用高效液相色谱串联质谱法(HPLC-MS/MS)定量检测尿液中AEA、SEA含量。使用受试者工作特征(ROC)曲线评价诊断模型的灵敏度与特异度。结果:与健康对照组相比较,NMIBC患者尿液样本中的AEA含量(P=0.0020<0.01)与SEA含量(P=0.0015<0.01)明显升高,具有显著统计学意义。建立ROC曲线,选择尿液AEA水平0.113 ng/ml作为cut-off值,此时AUC=0.8095,灵敏度85.7 1%,特异度66.67%;选择尿液SEA水平0.304 ng/ml作为cut-off值,此时AUC=0.9008,灵敏度90.48%,特异度75.00%。结论:1.NMIBC患者尿液中AEA与SEA含量与健康对照组相比显著升高,尿液AEA与SEA可作为NMIBC诊断的潜在生物标志物,具有较高灵敏度;2.NMIBC组与健康对照组尿液中SEA含量均高于AEA,用SEA作为诊断生物标志物更易检出。更多还原

【Abstract】 Objective: To quantitatively detect the content of endogenous cannabinoids in urine samples of patients with non-muscle-invasive bladder cancer(NMIBC)and healthy controls,and to verify the feasibility of endogenous cannabinoids such as arachidonic acid ethanolamine(AEA)and stearamide(SEA)as early non-invasive diagnostic markers for NMIBC,and to clarify the diagnostic performance.Methods: The urine samples of 21 patients with NMIBC diagnosed for the first time and 12 healthy control group who were hospitalized in Bethune Third Hospital of Jilin University from September 2021 to November 2022 were collected.All patients had no history of other malignant tumors,radiotherapy and chemotherapy and other benign diseases of the urinary system.Centrifuge the patient’s urine sample and use gradient elution to separate the substance to be tested;Use ESI ionization source to ionize the substance to be tested,and use high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)to quantitatively detect the content of AEA and SEA in urine.The sensitivity and specificity of the diagnostic model were evaluated using the subject working characteristic curve(ROC curve).Results: Compared with the healthy control group,the contents of AEA(P=0.0020<0.01)and SEA(P=0.0015<0.01)in urine samples of NMIBC patients were significantly higher,with significant statistical significance.The ROC curve was established and the urine AEA level of 0.113 ng/ml was selected as the cut-off value.AUC=0.8095,sensitivity 85.71%,specificity 66.67%;Select urine SEA level 0.304 ng/ml as the cut-off value.AUC=90.08%,sensitivity 90.48%,specificity 75.00%.Conclusion:1.The contents of AEA and SEA in urine of NMIBC patients were significantly higher than those of healthy control group;Urine AEA and SEA can be used as biomarkers for the diagnosis of NMIBC;2.The content of SEA in urine of NMIBC group and healthy control group is higher than that of AEA.It is easier to detect SEA as a potential diagnostic biomarker.更多还原