Glycoproteomics-based Liquid-biopsy LDT Development Service for Colorectal Cancer
Services Published Data
Importance of Glycosylation in Colorectal Cancer
Colorectal cancer (CRC) ranks as the second leading cause of cancer-related fatalities globally. It predominantly originates from adenomas that advance into carcinomas. Early detection and timely intervention can markedly enhance the prognosis and outcomes for individuals afflicted with CRC.
Glycosylation is a pivotal posttranslational modification of proteins, exerting a profound impact on biological processes. Aberrant glycosylation is a hallmark of various diseases and tumors. Noteworthy glycosylation variations associated with CRC encompass elevated levels of high-mannose type structures, heightened branching and core-fucosylation of N-glycans, and higher density of O-glycans. Mucin glycoproteins, prominent secretory products of the colon, undergo extensive O-glycosylation. In colon mucins, O-glycans such as core 1, 2, 3, and 4 demonstrate cancer-specific changes, often appearing truncated, sialylated, and fucosylated, thereby facilitating tumor progression and metastasis. Hence, employing LC–MS-driven glycoproteomic technology becomes paramount in comprehending the roles of aberrant glycosylation in the development and advancement of CRC.
Glycoproteomics-based Liquid-biopsy LDT Development for CRC at Creative Biolabs
Creative Biolabs has pioneered innovative Glycoproteomics-based Liquid-biopsy LDT Services to facilitate comprehensive analyses of N-glycosylation and O-glycosylation. Rooted in a bottom-up glycoproteomic approach, we have successfully established a sophisticated framework for the Analysis of Intact N-linked Glycopeptides. Our specialized LDT services also offer efficient methodologies for O-glycosylation profiling.
Fig.1 LDT development for O-glycosylation profiling
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Characterization of O-glycosylation
A crucial step in enhancing the specificity of O-glycosylation profiling involves the prior enzymatic cleavage of potential interferences arising from N-linked oligosaccharides. Subsequently, the enzymatically processed proteins undergo simultaneous alkaline-based O-glycan cleavage and quantitative permethylation, which is pivotal in maintaining the integrity of minor glycans. We leverage high-resolution MALDI-TOF/TOF mass spectrometry with robust computational tools renowned for predicting potential oligosaccharide structures. Additionally, a comprehensive statistical analysis is conducted to identify and elucidate the disparities between CRC samples and healthy controls.
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O-GlcNAc glycoproteomics analysis
Our laboratory has also pioneered O-GlcNAc glycoproteomic analysis. The principle is that covalently attaching a single GlcNAc monosaccharide to serine/threonine residues through O-GlcNAc glycosylation results in a molecular mass increase of 203.08Da. Mass spectrometry is capable of precisely detecting whether a corresponding mass shift has occurred, enabling the analysis of O-GlcNAc glycosylated peptide and their attachment sites.
Fig.2 LDT development for O-GlcNAc glycoproteomics.
Advantages of Our LDT Development
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Advanced methodology for N/O-glycosylation analysis
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Minimal sample volumes for O-glycosylation profiling
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High resolution and sensitivity of MS-based detection
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Robust tools for in-depth data analysis
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Professional technical team specialized in glycoproteomics
Published data
Colorectal cancer (CRC) is a prevalent form of cancer associated with a significant mortality rate globally. Timely screening is essential for enhancing patient survival rates. Currently, stool analysis, especially fecal immunochemical testing (FIT), has been widely applied for occult blood screening, but its sensitivity for precancerous lesions is insufficient, which limits the effectiveness of early detection. In this study, the authors used mass spectrometry technology to explore the expression of T antigen in precancerous lesions and colorectal cancer, providing important information for our understanding of disease-related fecal glycoproteomic changes. A total of 262 proteins were identified in the study, of which 67% showed changes in glycosylation patterns associated with cancer lesions. This study deeply analyzed the fecal glycoproteome and opened up a new direction for non-invasive CRC screening.
Fig.3 Glycoproteomics analysis protocol.1
Creative Biolabs offers cutting-edge glycoproteomics-based liquid biopsy LDT services, which hold great potential for characterizing abnormal N/O-glycosylation. This approach provides a promising pathway to gain a deeper understanding of CRC disease progression. For more detailed information, please don't hesitate to contact us or submit an inquiry directly.
Reference
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Soares, Janine, et al. "Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer." International Journal of Molecular Sciences 25.7 (2024): 3722. Distributed under Open Access license CC BY 4.0, without modification.
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