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.

Integrated proteo-genomic approach for early diagnosis and prognosis of cancer

“…During tumorigenesis the proteins of cancer signaling pathways can be post-translationally altered which could change their function; for example, by phosphorylation, acetylation and glycosylation each of which is capable of producing a functional shift that potentially affects disease development, progression and therapeutic response [13,14]. PTMs of proteins involved in signaling pathways are indispensable in many biological processes, and these PTMs have relevance to cancer pathogenesis and diagnosis [15][16][17].…”

Glycans and glycoproteins as specific biomarkers for cancer

“…Glycosylation is a substantial PTM with respect to size and occurrence, where more than 50% of proteins are estimated to be glycosylated [73,25]. For humans, this value may be larger, and for some fluids such as human milk, glycosylated proteins may be as high as 80% [74].…”

Global and site‐specific analysis of protein glycosylation in complex biological systems with Mass Spectrometry

“…Many secreted proteins are glycosylated, and secreted glycoproteins in body fluids may serve as excellent noninvasive biomarkers. One of the most important glycoproteomic applications in clinical samples is to discover effective disease biomarkers (Abd Hamid et al, 2008;Kaji et al, 2013;Benicky et al, 2014;Mayampurath et al, 2014;Pompach et al, 2014;Zhang et al, 2014;Song and Mechref, 2015;Cotton et al, 2017;Song et al, 2018). Unlike traditional strategies that screen a single or a small number of potential biomarker(s), monitoring a larger group of candidates using glycoproteomic approaches can often result in higher accuracy and specificity.…”