ArticleBiology2026
The Colorectal Cancer Glycocode: Tumour Sialylation Is Associated with an Immune-Excluded Phenotype and Distinct Therapeutic Signatures.
Article in Biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundTumour glycosylation regulates immune modulation and progression, but whether the CRC sialylome-the complete repertoire of sialylated glycans-defines a biologically distinct subtype remains unclear. We investigated how the "sugar code" shapes CRC biology, immunity, and therapeutic response.
methodsTranscriptomic data from three CRC cohorts (TCGA, Sidra-LUMC, and CPTAC-2; n = 988) were batch-corrected and integrated. Single-sample gene set enrichment analysis (ssGSEA) quantified sialyltransferase expression, sialic acid metabolism, EMT, MDR mechanisms, immune phenotypes, and Siglec-associated transcriptional signatures. GSEA, gene ontology enrichment analysis (GOEA), and drug ontology enrichment analysis (DOEA) characterised pathways and identified drug response-associated transcriptional signatures.
resultsHigh sialylome activity defined a genomically stable but clinically advanced CRC subset enriched for left-sided tumours, mucinous histology, MSI, and
conclusionsThe CRC sialylome is associated with tumour phenotypic variation, including immune-excluded states linked to Siglec-associated transcriptional signatures and patterns consistent with non-canonical drug resistance programmes. These findings position the "sugar code" as a central organising principle in CRC and identify glycan-directed therapies as a promising strategy for the targeting of this aggressive subtype.
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