ArticleCurrent medicinal chemistry2025
The Molecular Characteristics and Therapeutic Implications of O-glycan Synthesis in Pancreatic Cancer by Integrating Transcriptome and Single-cell Data.
Article in Current medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 3 citations in OpenAlex.
- Single-Cell Analysis Delineates Glutathione Metabolism-Related Gene Signatures in the Glioblastoma Microenvironment and Identifies GSTA4 as a Regulator of Malignant Behaviors.International journal of genomics · 2026Article
- The role of ATF3 in precision medicine of brain arteriovenous malformation: based on endothelial cell proliferation.Frontiers in immunology · 2025Article
- Single-cell atlas of endothelial cells in atherosclerosis: identifying C1 CXCL12+ ECs as key proliferative drivers for immunological precision therapeutics in atherosclerosis.Frontiers in immunology · 2025Article
- A stumbling block in pancreatic cancer treatment: drug resistance signaling networks.Frontiers in cell and developmental biology · 2024Review
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9 authors at 1 institution in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundGlycans constitute the primary components of proteins that regulate key carcinogenic processes in cancer progression. This study investigated the significance of O-glycan synthesis in the pathogenesis, outcome, and therapy of pancreatic cancer (PC).
methodsTranscriptomic data and clinical prognostic information of PC were acquired via TCGA and GEO databases. CSA database was used to obtain single-cell data of PC. The O-glycan biosynthesis signaling pathway and its related genes were acquired via the MSigDB platform. The nonnegative matrix factorization (NMF) clustering was utilized to construct the O-glycan biosynthesis- associated molecular subtypes in PC. The LASSO and Cox regression were utilized to build the prognostic prediction model. We utilized real-time quantitative PCR (qRT-PCR) to verify the expressed levels of model genes. Single-cell analysis was utilized to investigate the levels of target genes and O-glycan biosynthesis signaling pathway in the PC tumour microenvironment.
resultsWe obtained 30 genes related to O-glycan biosynthesis, among which 15 were associated with the prognosis of PC. All PC samples were grouped into two distinct molecular subtypes associated with O-glycan biosynthesis: OGRGcluster C1 and OGRGcluster C2, and compared to OGRGcluster C1. PCs in OGRGcluster C2 had a more advanced clinical stage and pathological grade, worse prognosis, and more active O-glycan biosynthesis function. Immune analysis indicated that naïve B cell, CD8+ T cell, memory-activated CD4+ T cell, and monocytes displayed remarkably higher infiltration levels in OGRGcluster C1 while resting NK cell, macrophages M0, resting dendritic cell, activated dendritic cell, and neutrophils exhibited markedly higher infiltration levels in OGRGcluster C2. OGRGcluster C1 exhibited higher sensitivities to drugs, such as cisplatin, irinotecan, KRAS(G12C) inhibitor-12, oxaliplatin, paclitaxel, and sorafenib. Besides, we built the O-glycan biosynthesis-related prognostic model (including SPRR1B, COL17A1, and ECT2) with a good prediction performance. SPRR1B, COL17A1, and ECT2 were remarkably highly expressed in PC tissues and linked to a poor outcome. Single-cell analysis revealed that O-glycan biosynthesis was observed only in PC, and consistent with this, the target genes were significantly enriched in PC.
conclusionWe first constructed molecular subtypes and prognostic models related to O-glycan biosynthesis in PC. It is clear that O-glycan biosynthesis is related to the development, prognosis, immune microenvironment, and treatment of PC. This provides new strategies for stratification, diagnosis, and treatment of PC patients.
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