Serum N-glycome characterization and anti-carbohydrate antibody profiling in oral squamous cell carcinoma patients

PLoS One

Rei-Jing Wang¹  Shih-Yun Guu¹  Tsung-Hsien Lin¹  Ling-Yi Hung¹  Su-Chieh Chang²  Peiwen Yu³  Wei-Chien Tang³  Po-Jan Fang³  Chuan-Fa Chang³ 

[1] Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan;Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan;OBI Pharma, Inc., Taipei, Taiwan, R.O.C

关键词: Cancer detection and diagnosis;    Antibodies;    Biomarkers;    Metastasis;    Glycosylation;    Carbohydrates;    Diagnostic medicine;    Prisms;   

DOI  :  10.1371/journal.pone.0178927

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Glycosylation is a protein post translational modification which plays important role in protein function, stabilization, trafficking, and turnover. Alteration of protein glycosylation is a common phenomenon during tumor progression, migration, invasion, angiogenesis, as well as metastasis. Hence, aberrant glycan structures and the induced corresponding anti-carbohydrate antibodies are potential biomarkers for cancer diagnosis. In this study, serum N-glycomes and anti-carbohydrate antibodies from normal populations and oral squamous cell carcinoma (OSCC) patients were investigated. Total serum proteins were lyophilized and subjected to chemical reduction, alkylation and trypsin digestion. The N-glycans were released, purified, permethylated, and analyzed using MALDI-TOF-Mass spectrometry. In addition, the serum anti-carbohydrate antibody profiles were also investigated by carbohydrate microarray. We found that the relative abundances of seven N-glycans were decreased or increased in serum of OSCC with diagnostic accuracy greater than 75%. The relative abundances of total tri-antennary and tetra-antennary glycans with varying degrees of fucosylation and sialylation were also increased in serum N-glycomes of OSCC. In an independent validation group of forty-eight OCCC patients, most of the high-molecular weight serum N-glycans showed significantly high sensitivity and specificity according to the identified cutoff values. Furthermore, the serum levels of two IgM antibodies were elevated accompanied with the decreased levels of nine IgG antibodies in patient serum. Taken together, these serum N-glycans and antibodies identified in this study should be considered as the candidates of potential biomarkers for OSCC diagnosis.

【 授权许可】

CC BY