结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性  

Profound Diversity of the N-Glycome from Microdissected Regions of Colorectal Cancer,Stroma,and Normal Colon Mucosa

作　　者：Di Wang Katarina Madunic Tao Zhang Guinevere S.M.Lageveen-Kammeijer Manfred Wuhrer 

机构地区：[1]Center for Proteomics and Metabolomics,Leiden University Medical Center,Leiden 2300 RC,Netherlands [2]Copenhagen Center for Glycomics,Department of Cellular and Molecular Medicine,University of Copenhagen,Copenhagen 2200,Denmark

出　　处：《Engineering》2023年第7期32-43,I0002,共13页工程（英文）

基　　金：supported by the China Scholarship Council.

摘　　要：Aberrant glycosylation is considered to be a hallmark of colorectal cancer(CRC),as demonstrated by various studies.While the N-glycosylation of cell lines and serum has been widely examined,the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures.To overcome these obstacles,we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous,stromal,and healthy mucosa cells.N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatographyelectrospray ionization tandem mass spectrometry,enabling the differentiation and structural characterization of isomeric species.In total,116 N-glycans were identified that showed profound differences in expression among cancer,stroma,and normal mucosa.In comparison with healthy mucosa,the cancer cells showed an increase in a2-6 sialylation and monoantennary N-glycans,as well as a decrease in bisected N-glycans.Moreover,specific sialylated and(sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers.In comparison with cancer,the stroma showed lower levels of oligomannosidic and monoantennary N-glycans,LewisA/X epitopes,and sulfation,as well as increased expression of(core-)fucosylation and a2-3 sialylation.Our study reveals the distinct N-glycomic profiles of different cell types in CRC and control tissues,proving the necessity of their separate analysis for the discovery of cancer-associated glycans.

关 键 词：Colorectal cancer Tumor Porous graphitized carbon liquid chromatography mass spectrometry N-glycomics Antibody response 

分 类 号：R735.3[医药卫生—肿瘤]