Unlocking the future of colorectal cancer detection: Advances in screening glycosylation-based biomarkers on biological mass spectrometry technology

•Potential glycan biomarkers identified for CRC diagnosis from 2016 to 2024.•Comparison and evaluation of current pretreatment methods for glycan detection.•Mechanistic insights into relative quantification of glycomics via LC-MS.•A systematic methodology for identifying potential glycan biomarkers in disease diagnosis. The incidence of colorectal cancer (CRC) is increasingly affecting younger populations, with its mortality rate rising annually. However, current clinical diagnostic techniques, such as colonoscopy and CEA antigen testing, remain invasive and prone to false-positive results, complicating early diagnosis and intervention. Glycosylation, a key post-translational modification, plays an essential role in cellular function, physiological regulation, and disease processes. In recent years, mass spectrometry technology has emerged as a powerful tool for screening glycan biomarkers, owing to its exceptional separation capabilities and sensitivity. This review encompasses the advancements in CRC glycan biomarkers from 2016 to 2024, with particular emphasis placed on N/O-glycan biomarkers identified through mass spectrometry. Nonetheless, the intrinsic low abundance and polyhydroxy nature of glycans hinder the specificity and sensitivity of current glycan biomarkers. To overcome these limitations, this article outlines pretreatment strategies for N/O-glycans, including glycan release, enrichment, purification, and derivatization, in conjunction with relative quantification techniques and high-throughput bioinformatics tools for biomarker screening. These strategies are anticipated to enhance the efficiency and precision of glycan biomarker identification through mass spectrometry. These advancements hold significant promise for enhancing CRC prevention, diagnosis, and treatment, thereby potentially improving patient outcomes and quality of life.