肺腺癌患者尿蛋白质组差异表达分析  

Analysis of differential expression of urinary proteome in patients with lung adenocarcinoma

作　　者：张民 陈振岗[2] 张文成[2] 史学军[3] 谢辉[3] 陈欢 王广舜[2] ZHANG Min;CHEN Zhen-gang;ZHANG Wen-cheng;SHI Xue-jun;XIE Hui;CHEN Huan;WANG Guang-shun(Tianjin Medical University Baodi Clinical College,Tianjin 300070,China)

机构地区：[1]天津医科大学宝坻临床学院,天津300070 [2]天津医科大学宝坻临床学院肿瘤外科,天津301800 [3]天津医科大学宝坻临床学院胸外科,天津301800 [4]西南医科大学临床医学系,四川泸州646000

出　　处：《武警后勤学院学报（医学版）》2019年第1期14-18,共5页Journal of Logistics University of PAP（Medical Sciences）

基　　金：吴阶平医学基金会临床科研专项资助基金项目(320-6799-15066)

摘　　要：【目的】探讨肺腺癌患者和健康志愿者尿蛋白质差异表达谱,寻找具有诊断价值的生物标志物。【方法】选取肺腺癌患者的尿标本13例,以22例健康志愿者尿标本作为对照组,利用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(sodium dodecyl sulfate-polyacrylamide gel electrophoresis,SDS-PAGE)技术和MS-Thermo-Orbitrap-Velos质谱对肺腺癌患者和健康志愿者尿进行蛋白质组学比较。采用酶联免疫吸附剂测定(enzyme linked immunosorbent assay,ELISA)验证质谱结果。应用受试者工作曲线(receiver operating characteristic curve,ROC)评估差异蛋白的临床价值。【结果】表达谱共鉴定出365个差异表达蛋白质,表达上调蛋白质185个、表达下调蛋白质180个,筛选出凝血与免疫通路相关蛋白质10个,ROC分析发现纤维蛋白溶酶原(plasminogen,PLG)和纤维蛋白原γ(Fibrinogen gamma chain,FGG)的敏感性和特异性均>80%,且曲线下面积(area under curve,AUC)>0.8。ELISA法实验结果与质谱结果趋势一致,FGG、PLG作为联合检测项目鉴别肺腺癌与健康人群的AUC为0.947,相对单一检测项目FGG(0.844)和PLG(0.934)的诊断效能更高(P<0.05)。但是,肺腺癌患者尿中FGG、PLG表达水平与患者的年龄、性别、吸烟、临床分期均无关。【结论】尿中FGG与PLG可以作为辅助肺腺癌诊断的标志物,但其与肺腺癌的各项临床参数之间无明显联系,需要进一步扩大样本进行分析。【Objective】To explore the differential expression profiles of urine protein in patients with lung adenocarcinoma and healthy volunteers, and search for valuable biomarkers for diagnosis.【Methods】Urinary samples were collected from 13 patients with lung adenocarcinoma and 22 healthy volunteers. The urine proteins were separated by Sodiumdode-cyl Sulfate Polyacrylamidegel Electrophoresis(1D SDS-PAGE). MS-Thermo-Orbitrap-Velos was applied to separate, extract and identify proteins in urinary samples from healthy people and patients with lung adenocarcinoma. The protein mass spectrometry was verified by ELISA. ROC(receiver operating characteristic curve) was used to determine the clinical value of urine proteins.【Results】Expression profile results showed that 365 differentially expressed proteins, 185 up-regulated proteins, 180 down-regulated proteins and 10 proteins related to blood coagulation and immune pathways were identified. ROC analysis indicated that the sensitivity and specificity of fiber protease(PLG) and fibrinogen γ(FGG) were both over 80%, and AUC was also over 0.8. The ELISA results were consistent with the trend of mass spectrometry. The AUC(0.947) of FGG and PLG, as a combined detection item, was higher than that of FGG(0.844) and PLG(0.934)(P<0.05). However, the expression levels of FGG and PLG in urine of patients with lung adenocarcinoma were not related to age, gender,smoking and clinical stage.【Conclusion】 FGG and PLG in urine can be used as markers to assist the diagnosis of lung adenocarcinoma. However, they show no significant correlation with various clinical parameters of lung adenocarcinoma, which requires further sample expansion for analysis.

关 键 词：肺腺癌 尿蛋白质组 纤维蛋白酶原 纤维蛋白原γ 

分 类 号：Q51[生物学—生物化学]