P2RY13+ dendritic cells correlate with enhanced antigen presentation and lymphocyte activation in lung adenocarcinoma

Background: Although P2RY13 has been implicated in immune regulation and prognosis in lung adenocarcinoma (LUAD), its specific cellular expression and functional mechanisms within the tumor microenvironment (TME) remain poorly understood. Methods: We integrated transcriptomic and clinical data from TCGA and GEO (GSE68465 and GSE31210), performed differential gene expression and functional enrichment analyses, and employed multiple algorithms including CIBERSORT, MCP-counter, quanTIseq, TIMER, and ESTIMATE to evaluate immune infiltration. Single-cell RNA sequencing data (GSE131907) was analyzed using Seurat to identify cell-type-specific expression, while CellChat was used to infer intercellular communication. Pathway activities were assessed with eight scoring methods (AUCell, UCell, AddModuleScore, GSVA, JASMINE, singscore, ssGSEA, viper) using MSigDB gene sets. Results: Our results demonstrated that P2RY13 was significantly downregulated in LUAD and predicted poor prognosis independently. It correlated positively with immune infiltration, particularly T cell markers. Single-cell analysis revealed specific enrichment in dendritic cells (DCs), with P2RY13(+) DCs more prevalent in normal tissues and exhibiting enhanced activity in antigen presentation and T cell activation. Conclusion: P2RY13 is an independent prognostic biomarker in LUAD, linked to an immunologically active TME. Its specific expression in dendritic cells enhances antigen presentation and T cell activation, underscoring its role in promoting anti-tumor immunity.