Cancer glycomics offers potential biomarkers and therapeutic targets in the framework of 3P medicine

Abstract

Glycosylation is one of the most important post-translational modifications (PTMs) in a protein, and is the most abundant and diverse biopolymer in nature. Glycans are involved in multiple biological processes of cancer initiation and progression, including cell-cell interactions, cell-extracellular matrix interactions, tumor invasion and metastasis, tumor angiogenesis, and immune regulation. As an important biomarker, tumor-associated glycosylation changes have been extensively studied. This article reviews recent advances in glycosylation-based biomarker research, which is useful for cancer diagnosis and prognostic assessment. Truncated O-glycans, sialylation, fucosylation, and complex branched structures have been found to be the most common structural patterns in malignant tumors. In recent years, immunochemical methods, lectin recognition-based methods, mass spectrometry (MS)-related methods, and fluorescence imaging-based in situ methods have greatly promoted the discovery and application potentials of glycomic and glycoprotein biomarkers in various cancers. In particular, MS-based proteomics has significantly facilitated the comprehensive research of extracellular glycoproteins, increasing our understanding of their critical roles in regulating cellular activities. Predictive, preventive and personalized medicine (PPPM; 3P medicine) is an effective approach of early prediction, prevention and personalized treatment for different patients, and it is known as the new direction of medical development in the 21st century and represents the ultimate goal and highest stage of medical development. Glycosylation has been revealed to have new diagnostic, prognostic, and even therapeutic potentials. The purpose of glycosylation analysis and utilization of biology is to make a fundamental change in health care and medical practice, so as to lead medical research and practice into a new era of 3P medicine.

Biomarkers for Early Cancer Detection: A Landscape View of Recent Advancements, Spotlighting Pancreatic and Liver Cancers

“…Hypermethylation of certain genes is associated with silencing tumor suppressor genes. , Cell-free DNA (cfDNA)/circulating tumor DNA (ctDNA ) shed by cancer cells into the bloodstream can be analyzed for genetic mutations and alterations associated with specific cancers. − MicroRNA (miRNA) involved in gene regulation can be used as biomarkers since their expression profiles can be altered in cancer. , Metabolites changes in metabolite profiles can indicate cancer-related alterations in metabolism, which rationalizes the use of metabolomic biomarkers. , Glycans are sugar molecules attached to proteins and lipids. Changes in glycosylation patterns on proteins and lipids can be associated with cancer and can serve as biomarkers. , Exosomes , small extracellular vesicles released by cells, can carry cancer-related molecules and are being investigated as potential biomarkers. , Imaging biomarkers for techniques like MRI, CT scans, and PET scans can reveal specific features associated with cancer, such as the size and location of tumors. PET scans use radioactive tracers to highlight areas with high metabolic activity, often indicating the presence of cancer.…”

“…Glycans are sugar molecules attached to proteins and lipids. Changes in glycosylation patterns on proteins and lipids can be associated with cancer and can serve as biomarkers. , …”

Potassium Channels, Glucose Metabolism and Glycosylation in Cancer Cells

“…Glycan structures found in cancer cells are directly related to cancer development, progression, and metastasis [22]. Sialic acid has a negative charge, which mediates intercellular interactions and signal transduction [166]. Overexpression of sugar antigens (e.g., sialyl-Lewis A antigen) is associated with poor survival in cancer patients [166].…”

Glycosylation and behavioral symptoms in neurological disorders

“…The diversity of glycomes and glycoproteomes is greatly increased by the various combinations of monosaccharides [ 17 ]. Recent advances in high-throughput glycomic technology have enabled systematic analysis of glycomes in preclinical and clinical studies, revealing abnormal glycan structures as hallmarks of cancer [ 18 ]. Thus, altered glycomes are considered potential biomarkers or therapeutic targets for many disorders[ 19 , 20 ].…”