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The Molecular Characteristics and Therapeutic Implications of O-glycan Synthesis in Pancreatic Cancer by Integrating
Binqian Huang1,2, Biao Zhang1, Jifeng Liu1
1Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Current Medicinal Chemistry
|April 25, 2024
Summary
This study reveals O-glycan biosynthesis is crucial in pancreatic cancer (PC) development and progression. Identifying molecular subtypes and a prognostic model offers new strategies for PC patient stratification, diagnosis, and treatment.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Glycans are key regulators of protein function and are implicated in cancer progression.
- O-glycan synthesis plays a significant role in the pathogenesis, prognosis, and therapeutic response of pancreatic cancer (PC).
Purpose of the Study:
- To investigate the role and significance of O-glycan biosynthesis in pancreatic cancer (PC).
- To identify molecular subtypes, develop prognostic models, and explore therapeutic sensitivities related to O-glycan biosynthesis in PC.
Main Methods:
- Utilized transcriptomic and clinical data from TCGA and GEO databases, alongside single-cell data from the CSA database.
- Employed nonnegative matrix factorization (NMF) for clustering, LASSO and Cox regression for prognostic model development, and qRT-PCR for gene expression validation.
- Conducted single-cell analysis to assess O-glycan biosynthesis pathway and target gene expression within the PC tumor microenvironment.
Main Results:
- Identified two distinct O-glycan biosynthesis-associated molecular subtypes (OGRGcluster C1 and C2) in PC, with C2 exhibiting more aggressive features and poorer prognosis.
- Revealed differential immune cell infiltration between subtypes and higher sensitivity of OGRGcluster C1 to several chemotherapeutic agents.
- Developed a prognostic model comprising SPRR1B, COL17A1, and ECT2, which demonstrated good prediction performance and were associated with poor outcomes in PC.
Conclusions:
- O-glycan biosynthesis is intricately linked to the development, prognosis, immune microenvironment, and treatment response in pancreatic cancer.
- The identified molecular subtypes and prognostic model provide novel avenues for stratifying PC patients for improved diagnosis and targeted therapies.
