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: PXD055957 | Pride | 2025-06-16

REPOSITORIES: Pride