Abstract

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.

Highlights

  • Oral squamous cell carcinoma (OSCC) is the tumor that grows on the lips, tongue, floor of the oral cavity, hard and soft palate, sinuses, salivary glands, tonsils, pharynx and the peripheral tissue of the mouth

  • We found that the relative abundances of fucosylated, tri-antennary and tetra-antennary glycans were significantly increased in the OSCC patient serums compared with normal human serums (Table 1)

  • We found that the relative abundance of fucosylated tetra-sialylated tetra-antennary glycan (m/z = 4587.27), fucosylated tri-sialylated tetra-antennary glycan (m/z = 4675.32), tri-antennary glycans, and tetra-antennary glycans showed significant differences in stages I to IV compared with normal control (S2 Fig)

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Summary

Introduction

Oral squamous cell carcinoma (OSCC) is the tumor that grows on the lips, tongue, floor of the oral cavity, hard and soft palate, sinuses, salivary glands, tonsils, pharynx and the peripheral tissue of the mouth. It is one of the most commonly diagnosed cancer in the world. The relative prevalence of OSCC increases about 110% over the past 15 years because of the habit of smoking, drinking and betel quid chewing [2, 3]. The five-year-survival rate of OSCC is unsatisfied in late stage (52.2% in stage III and 32.8% in stage IV) (Bureau of Health Promotion Department of Health, R.O.C., Taiwan).

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