Abstract
BackgroundMost glycomics studies have focused on understanding disease mechanisms and proposing serum markers for various diseases, yet the influence of ethnic variation on the identified glyco-biomarker remains poorly addressed. This study aimed to investigate the inter-ethnic serum N-glycan variation among US origin control, Japanese, Indian, and Ethiopian healthy volunteers.MethodsHuman serum from 54 healthy subjects of various ethnicity and 11 Japanese hepatocellular carcinoma (HCC) patients were included in the study. We employed a comprehensive glycoblotting-assisted MALDI-TOF/MS-based quantitative analysis of serum N-glycome and fluorescence HPLC-based quantification of sialic acid species. Data representing serum N-glycan or sialic acid levels were compared among the ethnic groups using SPSS software.ResultsTotal of 51 N-glycans released from whole serum glycoproteins could be reproducibly quantified within which 33 glycoforms were detected in all ethnicities. The remaining N-glycans were detected weakly but exclusively either in the Ethiopians (13 glycans) or in all the other ethnic groups (5 glycans). Highest abundance (p < 0.001) of high mannose, core-fucosylated, hyperbranched/hypersialylated N-glycans was demonstrated in Ethiopians. In contrast, only one glycan (m/z 2118) significantly differed among all ethnicities being highest in Indians and lowest in Ethiopians. Glycan abundance trend in Ethiopians was generally close to that of Japanese HCC patients. Glycotyping analysis further revealed ethnic-based disparities mainly in the branched and sialylated structures. Surprisingly, some of the glycoforms greatly elevated in the Ethiopian subjects have been identified as serum biomarkers of various cancers. Sialic acid level was significantly increased primarily in Ethiopians, compared to the other ethnicities.ConclusionThe study revealed ethnic-specific differences in healthy human serum N-glycome with highest abundance of most glycoforms in the Ethiopian ethnicity. The results strongly emphasized the need to consider ethnicity matching for accurate glyco-biomarker identification. Further large-scale study employing various ethnic compositions is needed to verify the current result.
Highlights
Glycosylation, the process in which sugars are attached to proteins or lipids, is the most abundant and complex post-translational process, causing immense structural and functional variabilities in majority of eukaryotic cell proteins [1, 2]
Most glycomics studies have focused on understanding disease mechanisms and proposing serum markers for various diseases, yet the influence of ethnic variation on the identified glyco-biomarker remains poorly addressed
Human serum from 54 healthy subjects of various ethnicity and 11 Japanese hepatocellular carcinoma (HCC) patients were included in the study
Summary
Glycosylation, the process in which sugars are attached to proteins or lipids, is the most abundant and complex post-translational process, causing immense structural and functional variabilities in majority of eukaryotic cell proteins [1, 2]. In contrast to nucleic acids and proteins, biosynthesis of glycans is not template-driven but, rather, is a result of a complex network of metabolic and enzymatic reactions Because of this and subsequent methodological difficulties, the field of glycomics has been lagging behind genomics and proteomics [9, 10]. Tremendous advancements in analytical techniques and bioinformatics platforms have recently revolutionized the area, enabling comprehensive profiling of glycans and glycoproteins to be released from various biological samples [11,12,13] and suggested as biomarkers Bringing these glycan or glycoprotein markers to clinical practice has been hindered as their potential to distinguish cases from controls or disease stages seems to be inadequate and varies from country to country population wise, complicating their validity and clinical utility [14, 15]. This study aimed to investigate the inter-ethnic serum N-glycan variation among US origin control, Japanese, Indian, and Ethiopian healthy volunteers
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