ArticleNPJ precision oncology2026
AI-enabled single-cell dissection of the palmitoylation landscape identifies a multicellular prognostic program in gastric cancer.
Article in NPJ precision oncology, 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
Gastric cancer remains highly lethal, yet how protein S-palmitoylation shapes tumour ecosystems and clinical outcome is unclear. We integrated single-cell RNA sequencing (119,931 cells from 25 gastric tumours) with spatial transcriptomics and bulk cohorts to delineate palmitoylation-linked states across malignant, immune, and stromal compartments. A palmitoylation-high malignant programme partitioned into three metastasis-enriched subclusters with increased fatty-acid metabolism and Ras-MAPK signalling and predicted worse survival. Spatial mapping and ligand-receptor inference revealed co-localised niches where palmitoylation-high tumour cells interacted with immunosuppressive myeloid cells and distinct CAF subsets, with strengthened pro-angiogenic and pro-fibrotic cues. We derived and validated an 87-gene multicellular palmitoylation signature for risk stratification, and higher scores were consistently associated with adverse outcomes in external cohorts. Drug-response modelling highlighted vulnerabilities involving the HSP90-PI3K/MAPK axis. Functional assays and xenografts confirmed SH3BGRL as a key driver within this poor-prognosis programme.
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