Chemical Proteomic Approach for In-Depth Glycosylation Profiling of Plasma Carcinoembryonic Antigen in Cancer Patients

Chen, Jin1,2,3; Yang, Lijun4,5; Li, Chang1,2; Zhang, Luobin4; Gao, Weina1,2; Xu, Ruilian4; Tian, Ruijun1,2

2023-11-01

10.1016/j.mcpro.2023.100662

MOLECULAR & CELLULAR PROTEOMICS   影响因子和分区

1535-9484

Carcinoembryonic antigen (CEA) of human plasma is a biomarker of many cancer diseases, and its N-glycosyla-tion accounts for 60% of molecular mass. It is highly desirable to characterize its glycoforms for providing additional dimension of features to increase its perfor-mance in prognosis and diagnosis of cancers. However, to systematically characterize its site-specific glycosylation is challenging because of its low abundance. Here, we developed a highly sensitive strategy for in-depth glyco-sylation profiling of plasma CEA through chemical prote-omics combined with multienzymatic digestion. A trifunctional probe was utilized to generate covalent bond of plasma CEA and its antibody upon UV irradiation. As low as 1 ng/ml CEA in plasma could be captured and digested with trypsin and chymotrypsin for intact glyco-peptide characterization. Twenty six of 28 potential N-glycosylation sites were well identified, which were the most comprehensive N-glycosylation site characterization of CEA on intact glycopeptide level as far as we known. Importantly, this strategy was applied to the glycosylation analysis of plasma CEA in cancer patients. Differential site-specific glycoforms of plasma CEA were observed in patients with colorectal cancers (CRCs) and lung cancer. The distributions of site-specific glycoforms were different as the progression of CRC, and most site-specific glyco-forms were overexpressed in stage II of CRC. Overall, we established a highly sensitive chemical proteomic method to profile site-specific glycosylation of plasma CEA, which should generally applicable to other well-established cancer glycoprotein biomarkers for improving their can-cer diagnosis and monitoring performance.

SCI

英语

第一 ; 通讯

China State Key Basic Research Program["2021YFA1301601","2020YFE0202200","2021YFA1302603","2022YFC3401104","2021YFA1301602"] ; National Natural Science Foundation of China["22104047","22004049","32171433","81900034","22125403","22004056"] ; Shenzhen Innovation of Science and Technology Commission["JSGGZD20220822095200001","JCYJ20200109141212325","JCYJ20210324120210029"] ; Guangdong province[2019B151502050] ; Natural Science Foundation of Fujian Province[2021J01255]

Biochemistry & Molecular Biology

Biochemical Research Methods

WOS:001105562900001

ELSEVIER

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Southern Univ Sci & Technol, Dept Chem, Shenzhen, Peoples R China
2.Southern Univ Sci & Technol, Res Ctr Chem Biol & Om Anal, Sch Sci, Shenzhen, Peoples R China
3.Fujian Med Univ, Affiliated Hosp 2, Clin Ctr Mol Diag & Therapy, Quanzhou, Fujian, Peoples R China
4.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Oncol, Shenzhen, Peoples R China
5.Jinan Univ, Affiliated Hosp 1, Guangzhou, Peoples R China

Chen, Jin,Yang, Lijun,Li, Chang,et al. Chemical Proteomic Approach for In-Depth Glycosylation Profiling of Plasma Carcinoembryonic Antigen in Cancer Patients[J]. MOLECULAR & CELLULAR PROTEOMICS,2023,22(11).

Chen, Jin.,Yang, Lijun.,Li, Chang.,Zhang, Luobin.,Gao, Weina.,...&Tian, Ruijun.(2023).Chemical Proteomic Approach for In-Depth Glycosylation Profiling of Plasma Carcinoembryonic Antigen in Cancer Patients.MOLECULAR & CELLULAR PROTEOMICS,22(11).

Chen, Jin,et al."Chemical Proteomic Approach for In-Depth Glycosylation Profiling of Plasma Carcinoembryonic Antigen in Cancer Patients".MOLECULAR & CELLULAR PROTEOMICS 22.11(2023).