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Systematic Pan-Cancer Characterization of ST3GAL4 Reveals Its Prognostic and Immunologic Associations.

Fushu Luo^1,2, Xiaoshun Sun^1,2, Changwu Wu^1,2

¹Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.

|May 4, 2026

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The sialyltransferase ST3GAL4 is dysregulated across many cancers, correlating with poor prognosis and an immunosuppressive tumor microenvironment. This study maps its pan-cancer landscape, linking sialylation to immune evasion and suggesting ST3GAL4 as a therapeutic target.

Area of Science:

Glycoscience
Cancer Biology
Immunology

Background:

Sialylation is a critical glycosylation process influencing tumor progression and immune evasion.
The role of sialyltransferase ST3GAL4 in cancer is not fully understood across diverse cancer types.

Purpose of the Study:

To define the pan-cancer landscape and systemic associations of ST3GAL4.
To investigate the relationship between ST3GAL4 expression and tumor microenvironment characteristics.

Main Methods:

Integrated multi-omics analysis (transcriptomics, proteomics, genomics, methylation) using TCGA, CPTAC, and GTEx data.
Evaluation of immune cell infiltration and associations using TIMER2.0 and TISIDB.
Experimental validation via immunofluorescence staining of ST3GAL4 protein in tumor specimens.

Keywords:

ST3GAL4 TCGA glycosylation immune infiltration pan-cancer prognostic marker

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Main Results:

ST3GAL4 shows widespread, lineage-specific dysregulation, linked to adverse prognosis and genomic instability.
Elevated ST3GAL4 correlates with increased cancer-associated fibroblasts and endothelial cells, but decreased cytotoxic T-cells.
Functional enrichment points to ST3GAL4's role in glycosphingolipid metabolism and glycan biosynthesis.

Conclusions:

This study presents a comprehensive pan-cancer atlas of ST3GAL4, highlighting its link to aggressive cancer phenotypes.
ST3GAL4 is associated with an immunosuppressive tumor microenvironment and core glycosylation pathways.
ST3GAL4 emerges as a potential target connecting sialylation to immune evasion, warranting further investigation.