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Updated: Feb 17, 2026

Glycomics-Guided Glycoproteomics Facilitates Comprehensive Profiling of the Glycoproteome in Complex Tumor Microenvironments
Published on: February 7, 2025
O-glycosylation in Cancer: Emerging Paradigms and Prospects for Precision Oncology
Junhao Wei1,2, Shengbao Hu1, Wanfang Chen3
1Department of Laboratory Medicine, Jiayu Hospital, Zhongnan Hospital of Wuhan University (People's Hospital of Jiayu County), Xianning 437200, Hubei, China.
Abstract:
O-glycosylation is a key post-translational modification that profoundly shapes tumor biology by regulating cell proliferation, metastasis, and immune evasion. Aberrant O-glycosylation features truncated glycans such as Tn and sialyl-Tn antigens together with dysregulated glycosyltransferases and promotes oncogenesis in diverse malignancies. This review summarizes recent progress in elucidating the role of O-glycosylation in cancer with emphasis on its effects on cell-surface glycoproteins, intracellular signaling pathways, and emerging RNA modifications. Integration of multi-omics data and machine learning has transformed tumor classification and prognosis prediction through distinct glycosylation signatures and now supports personalized treatment strategies. Newly discovered O-glycosylation of RNA reveals additional regulatory layers and broadens the field of glycosylation research. Targeted interventions including glycosyltransferase inhibitors, gene editing, and combination with immunotherapy demonstrate promising therapeutic potential. Advanced high-throughput tools especially mass spectrometry and enzymatic release methods accelerate biomarker discovery and target validation. Collectively, this review underscores the multifaceted impact of O-glycosylation on cancer progression and treatment response while highlighting the urgent need for continued interdisciplinary collaboration to translate these findings into precision oncology and better patient outcomes.
Insights
O-glycosylation, a key cancer process, involves altered cell signaling and immune evasion. New insights into RNA modifications and targeted therapies offer hope for precision oncology.
Area of Science:
- Biochemistry and Molecular Biology
- Cancer Research
- Glycomics
Background:
- O-glycosylation is a critical post-translational modification influencing tumor progression, metastasis, and immune evasion.
- Aberrant O-glycosylation, characterized by truncated glycans (Tn, sialyl-Tn) and dysregulated glycosyltransferases, drives oncogenesis across various cancers.
Purpose of the Study:
- To review recent advancements in understanding O-glycosylation's role in cancer.
- To highlight O-glycosylation's impact on cell-surface glycoproteins, intracellular signaling, and RNA modifications.
- To discuss the integration of multi-omics and machine learning for cancer classification and personalized treatment.
Main Methods:
- Literature review of recent progress in O-glycosylation research in cancer.
- Analysis of multi-omics data and machine learning applications in glycosylation signature identification.
- Examination of emerging RNA modification studies and advanced high-throughput tools (mass spectrometry, enzymatic methods).
Main Results:
- O-glycosylation significantly impacts cancer cell proliferation, metastasis, and immune evasion.
- Aberrant glycosylation patterns are linked to oncogenesis and can serve as distinct prognostic signatures.
- Newly discovered O-glycosylation of RNA adds regulatory complexity, broadening the scope of glycosylation research.
- Targeted interventions like glycosyltransferase inhibitors and combination therapies show therapeutic promise.
Conclusions:
- O-glycosylation plays a multifaceted role in cancer progression and treatment response.
- Integration of advanced tools and interdisciplinary collaboration is crucial for translating findings into precision oncology.
- Further research into O-glycosylation, including RNA modifications, is essential for improving patient outcomes.
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