Dataset Information

N-Glycoproteomic analysis reveals novel mechanism and clinical relevance in Colorectal Cancer

ABSTRACT: Glycosylation is largely involved in development and progression of cancer and provides multiple novel targets for diagnostic application and therapeutic strategies. Recent advances in methods for enrichment and mass spectrometric interpreting of intact N-glycoprotein contribute to large-scale clinical glycoproteomics datasets generation, whereas systematic interpretation of these data remains challenging due to the complexity and unstable nature of N-glycosylation modifications. In this study, we mapped the glycoproteome of 45 untreated, resectable colorectal cancer (CRC) tumors, together with their normal adjacent tissues, quantifying over 7,000 N-linked glycoproteins by employing advanced mass spectrometry and high-throughput data analysis. Protein N-sialylation and N-high-mannosylation were revealed to be the most commonly altered modifications in our qualitative and quantitative analysis. Furthermore, we constructed a dynamic N-glycan-site-protein-signaling pathway network based on the N-glycan profiles, highlighting the crucial roles of glycosylated proteins in immune response and various cellular processes. For a comprehensive study on N-glycan functions in CRC, we established a robust scoring system for the combined glycoform profiles, which could potentially be used for biomarker and drug target discovery. In addition, our study revealed FUCA1 and ERO1A as significant dysregulated glycosyltransferases closely related to CRC development and identified APMAP-N196 glycosylation, a potential biomarker for CRC prediction and therapy response monitoring. Overall, the findings underscore the importance of glycosylation dynamics in CRC progression and pave the way for early diagnosis and personalized therapies.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon

DISEASE(S): Colon Cancer

SUBMITTER: He Huang

LAB HEAD: He Huang

PROVIDER: PXD055935 | Pride | 2025-06-16

REPOSITORIES: Pride

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Publications

Deciphering the Metabolic Impact and Clinical Relevance of N-Glycosylation in Colorectal Cancer through Comprehensive Glycoproteomic Profiling.

Liu Guobin G Chen Lu L Zhao Jingxiang J Jiang Yue Y Guo Yarong Y Mao Xiang X Ren Xuelian X Liu Kun K Mei Qi Q Li Qunyi Q Huang He H

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20250426 21

Colorectal cancer (CRC) progression is driven by complex metabolic alterations, including aberrant N-glycosylation patterns that critically influence tumor development. However, the metabolic and functional roles of N-glycosylation in CRC remain poorly understood. Herein, comprehensive proteomic and N-linked intact glycoproteomics analyses are performed on 45 CRC tumors, and normal adjacent tissues (NATs) are matched, identifying 7125 intact N-glycopeptides from 704 glycoproteins. Through analys ...[more]

PMID: 40285620

Similar Datasets

Project description:Various cancers such as colorectal cancer (CRC) are associated with alterations in protein glycosylation. CRC cell lines are frequently used to study these (glyco)biological changes and their mechanisms. However, differences between CRC cell lines with regard to their glycosylation have hitherto been largely neglected. Here, we comprehensively characterized the N-glycan profiles of 25 different CRC cell lines, derived from primary tumors and metastatic sites, in order to investigate their potential as glycobiological tumor model systems and to reveal glycans associated with cell line phenotypes. We applied an optimized, high-throughput membrane-based enzymatic glycan release for small sample amounts. Released glycans were derivatized to stabilize and differentiate between a2,3- and a2,6-linked N-acetylneuraminic acids, followed by N-glycosylation analysis by MALDI-TOF(/TOF)-MS. Our results showed pronounced differences between the N-glycosylation patterns of CRC cell lines. CRC cell line profiles differed from tissue-derived N-glycan profiles with regard to their high-mannose N-glycan content but showed a large overlap for complex type N-glycans, supporting their use as a glycobiological cancer model system. Importantly, we could show that the high-mannose N-glycans did not only occur as intracellular precursors but were also present at the cell surface. The obtained CRC cell line N-glycan features were not clearly correlated with mRNA expression levels of glycosyltransferases, demonstrating the usefulness of performing the structural analysis of glycans. Finally, correlation of CRC cell line glycosylation features with cancer cell markers and phenotypes revealed an association between highly fucosylated glycans and CDX1 and/or villin mRNA expression that both correlate with cell differentiation. Together, our findings provide new insights into CRC-associated glycan changes and setting the basis for more in-depth experiments on glycan function and regulation.

Project description:This data set was downloaded from MetaboLights (http://www.ebi.ac.uk/metabolights/) accession number MTBLS227 Abstract:"Various cancers such as colorectal cancer (CRC) are associated with alterations in protein glycosylation. CRC cell lines are frequently used to study these (glyco)biological changes and their mechanisms. However, differences between CRC cell lines with regard to their glycosylation have hitherto been largely neglected. Here, we comprehensively characterized the N-glycan profiles of 25 different CRC cell lines, derived from primary tumors and metastatic sites, in order to investigate their potential as glycobiological tumor model systems and to reveal glycans associated with cell line phenotypes. We applied an optimized, high-throughput membrane-based enzymatic glycan release for small sample amounts. Released glycans were derivatized to stabilize and differentiate between a2,3- and a2,6-linked N-acetylneuraminic acids, followed by N-glycosylation analysis by MALDI-TOF(/TOF)-MS. Our results showed pronounced differences between the N-glycosylation patterns of CRC cell lines. CRC cell line profiles differed from tissue-derived N-glycan profiles with regard to their high-mannose N-glycan content but showed a large overlap for complex type N-glycans, supporting their use as a glycobiological cancer model system. Importantly, we could show that the high-mannose N-glycans did not only occur as intracellular precursors but were also present at the cell surface. The obtained CRC cell line N-glycan features were not clearly correlated with mRNA expression levels of glycosyltransferases, demonstrating the usefulness of performing the structural analysis of glycans. Finally, correlation of CRC cell line glycosylation features with cancer cell markers and phenotypes revealed an association between highly fucosylated glycans and CDX1 and/or villin mRNA expression that both correlate with cell differentiation. Together, our findings provide new insights into CRC-associated glycan changes and setting the basis for more in-depth experiments on glycan function and regulation."

Project description:Alterations in glycosylation are seen in many types of cancer, including colorectal cancer (CRC). CRC is known to display glycosylation alterations. Glycans, the sugar moieties of glycoconjugates, are involved in many important functions relevant to cancer, such as cell signaling and adhesion, and may can be of value as biomarkers. In this study, we have used mass spectrometry to analyze the N-glycan profiles of 35 CRC tissue samples from patients with tumors in the right or left colon and 10 healthy tissue samples from non-CRC patients who underwent operations for other reasons. The tumor samples were divided into groups depending on tumor location (right or left colon) and stage (II or III), while the healthy samples were divided into right or left side of the colon. The levels of neutral and acidic N-glycan compositions and glycan classes were analyzed in a total of ten different groups. Surprisingly, there were no significant differences in glycan levels when all right- and left-sided CRC samples were compared, and few differences (such as in the abundance of the neutral N-glycan H3N5) were seen when the samples were divided according to both location and stage. Multiple significant differences were found in the levels of glycans and glycan classes when stage II and III samples were compared, and these glycans could be of value as candidates for new markers of cancer progression. In order to validate our findings, we analyzed healthy tissue samples from the right and left colon and found no significant differences in the levels of any of the glycans analyzed, confirming that our findings when comparing CRC samples from the right and left colon are not due to normal variations in the levels of glycans between the healthy right and left colon. Additionally, the levels of the acidic glycans H4N3F1P1, H5N4F1P1, and S1H5N4F1 were found to change in a cancer-specific but colon location-nonspecific manner, indicating that CRC affects glycan levels in similar ways, regardless of tumor location.

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