肺癌与肺良性疾病特异血清免疫炎性蛋白质N-糖基化修饰差异  

Study on the differences in N-glycosylation of disease-specific immune and inflammatory proteins between lung cancer and lung benign disease

作　　者：杜钰莹 王悦[2] 赖治臻 田志新[2] 李智立[1] DU Yu-ying;WANG Yue;LAI Zhi-zhen;TIAN Zhi-xin;LI Zhi-li(Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005;Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science &Engineering, Tongji University, Shanghai 200092, China)

机构地区：[1]中国医学科学院基础医学研究所,北京协和医学院基础学院,生物物理及结构生物学系,北京100005 [2]同济大学化学科学与工程学院,上海市化学品分析风险评估与控制重点实验室,上海200092

出　　处：《基础医学与临床》2020年第8期1096-1102,共7页Basic and Clinical Medicine

基　　金：中国医学科学院医学与健康科技创新工程(2018-I2M-AI-014)。

摘　　要：目的探索肺癌与肺良性疾病特异血清免疫炎性蛋白质N-糖基化修饰差异。方法应用非变性聚丙烯酰胺凝胶电泳(native-PAGE)从肺腺癌和慢性肺炎患者血清中分离得到一组疾病特异的血清免疫炎性蛋白质复合物(IIRPCs),经胶内酶解、石墨相氮化碳富集分离得到完整糖肽。应用高效液相色谱-串联质谱(HPLC-MS/MS)技术,结合GPSeeker数据库检索软件进行糖肽鉴定。结果共鉴定了来自12种蛋白质的89种糖肽,其中21种仅与肺良性疾病相关,38种仅与肺癌相关。89种糖肽中包括63种糖型,其中10种为肺良性疾病特有糖型,21种为肺癌特有糖型。两种疾病的特有糖型在其结构和连接位点上均存在差异。结论发现了两种疾病血清特异免疫炎性蛋白质N-糖基化修饰的差异,为糖基化修饰在慢性疾病的诊断、预后评估和分子机制等方面的研究提供了新视角。Objective To define the differences in N-glycosylation of disease-specific immune and inflammatory proteins between lung cancer and benign lung disease.Methods A group of disease-specific serum immunoin-flammation-related protein complexes(IIRPCs)were isolated from the sera of two patients with lung adenocarcinoma and chronic pneumonia,by native-polyacrylamide gel electrophoresis(native-PAGE).The intact glycopeptides were obtained by in-gel trypsin digestion and then enriched by graphite phase carbon nitride.The glycopeptides were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)coupled with GPSeeker database software.Results Totally 89 glycopeptides from 12 proteins were identified,21 of which only existed in benign lung disease and 38 only be found in lung cancer samples.Ten of the 63 unique glycoforms from the 89glycopeptides only existed in benign lung disease and only 21 were found in lung cancer.Conclusions The specific differences in N-glycosylation of disease-specific immune and inflammatory proteins are found between benign lung disease and lung cancer.These findings indicate that N-glycosylation may function as potential biomarker applied in diagnosis and prognosis of chronic diseases as well as a novel sight to molecular mechanism of chronic diseases.

关 键 词：疾病特异蛋白质 疾病特异糖肽 疾病特异糖型 肺疾病 

分 类 号：Q51[生物学—生物化学]