Clinical application of quantitative glycomics

Abstract

Aberrant glycosylation has been associated with many diseases. Decades of research activities have reported many reliable glycan biomarkers of different diseases which enable effective disease diagnostics and prognostics. However, none of the glycan markers have been approved for clinical diagnosis. Thus, a review of these studies is needed to guide the successful clinical translation. Area covered: In this review, we describe and discuss advances in analytical methods enabling clinical glycan biomarker discovery, focusing only on studies of released glycans. This review also summarizes the different glycobiomarkers identified for cancers, Alzheimer's disease, diabetes, hepatitis B and C, and other diseases. Expert commentary: Along with the development of techniques in quantitative glycomics, more glycans or glycan patterns have been reported as better potential biomarkers of different diseases and proved to have greater diagnostic/diagnostic sensitivity and specificity than existing markers. However, to successfully apply glycan markers in clinical diagnosis, more studies and verifications on large biological cohorts need to be performed. In addition, faster and more efficient glycomic strategies need to be developed to shorten the turnaround time. Thus, glycan biomarkers have an immense chance to be used in clinical prognosis and diagnosis of many diseases in the near future.

Keywords: Biomarker; cancer and other diseases; clinical application; diagnosis; glycomics; prognosis.

Figure 1.. N-glycan profiling of tissue microarray (TMA) distinguished liver cancer from normal tissues using MALDI imaging.

A liver TMA purchased by BioChain consisting of 2 tumor tissue cores and one normal tissue core from 16 patients was imaged (200 μm raster). The H&E (a) provides the TMA location (red letters and numbers) and classifies whether the row is tumor (green bar) or non-tumor (red bar). M/z = 2393.95 (c) and m/z 1743.64 (d) were able to distinguish between hepatocellular carcinoma and uninvolved liver tissue. An overlay of these ion demonstrates that m/z = 2393.95 is elevated in tumor tissue and m/z = 1743.64 is elevated in normal tissue (b). Reproduced with permission from [95].

Figure 2.. N-glycan profiling of a large cohort revealed the differential glycan expressions between CRC patients and healthy people using HILIC-UPLC.

(a) A representative chromatogram from human plasma N-glycome and peak assignments from the CRC cohort. Significant peaks (found on training set of 625 patients vs. 468 control) are colored in red (increased in CRC) and blue (decreased in CRC). ‘*’ indicates one of the top five peak abundance changes (i.e. lowest p-value). (b) Significant peaks are marked decreased (blue) or increased (red) in all CRC and four stages of CRC. Reproduced with permission from [119].

Figure 3.. Differentiation of gastric cancer and healthy control groups using O-glycan profiles.

(a) MS spectra (average of retention time ranging from 19.14–20.88 min) of O-glycans from serum of normal controls (upper panel) and gastric cancer patients (lower panel). Proposed O-glycan structures were based on LC-MS/MS and the biosynthesis pathway of glycobiology. (Red triangle, fucose; yellow circle, galactose; yellow square, N-acetylgalactosamine; blue square, N-acetylglucosamine; purple diamond, N-acetylneuraminic acid; PMP, 1-phenyl-3-methyl-5-pyrazolone; 2× and 3× indicate the number of fucose.) (b) PLS-DA score plot based on LC-MS data of O-glycans derived from gastric cancer (red circles) and healthy control (black squares) serum samples. (c) ROC analysis of the significantly altered O-glycans in the patient serum samples (AUC = 0.97). Reproduced with permission from [160].

Figure 4.. Profiling of isomeric glycans derived from the blood serum of HCC and cirrhotic patients.

Extracted ion chromatograms of biantennary monosialylated branch-fucosylated glycan linkage isomers derived from (a) cirrhotic and (b) hepatocellular carcinoma patients. (c) MS/MS interpretation of biantennary monosialylated branch-fucosylated glycan. Reproduced with permission from [52].

Figure 5.. Venn diagram of N- and O-glycan biomarkers summarized from cancers that have most potential N-glycan biomarkers reported.

(a) Potential N-glycan biomarkers of top 6 cancers. (b) Potential O-glycan biomarkers