Mass spectrometry-based N-glycoproteomics for cancer biomarker discovery

Abstract

Glycosylation is estimated to be found in over 50% of human proteins. Aberrant protein glycosylation and alteration of glycans are closely related to many diseases. More than half of the cancer biomarkers are glycosylated-proteins, and specific glycoforms of glycosylated-proteins may serve as biomarkers for either the early detection of disease or the evaluation of therapeutic efficacy for treatment of diseases. Glycoproteomics, therefore, becomes an emerging field that can make unique contributions to the discovery of biomarkers of cancers. The recent advances in mass spectrometry (MS)-based glycoproteomics, which can analyze thousands of glycosylated-proteins in a single experiment, have shown great promise for this purpose. Herein, we described the MS-based strategies that are available for glycoproteomics, and discussed the sensitivity and high throughput in both qualitative and quantitative manners. The discovery of glycosylated-proteins as biomarkers in some representative diseases by employing glycoproteomics was also summarized.

Keywords: Disease proteomics; Glycosylation; Mass spectrometry.

Figure 1

Strategy of the mass spectrometry-based N-glycoproteome.

Figure 2

The common enrichment strategies for N-glycoprotein/glycopeptide.

Figure 3

The common quantitative aim and related strategies for N-glycoproteome. (a) Interpreting alterations in glycoproteomics. ① Changes in site specific glycosylation level; ② Changes in protein expression level; ③ Changes in glycosylation occupancy level. Glycosylation site is depicted by a filled red circle. (b) Specific quantitative strategies for different goals. “D” denote disease sample, “C” denote control sample.