ADGRG1/GPR56 across human cancers: genomic, prognostic, immune and pharmacogenomic insights

Purpose: ADGRG1 encodes GPR56, an adhesion G protein-coupled receptor involved in cell–matrix communication, immune-cell biology and tumor-context-dependent signaling. This study evaluated the genomic, transcriptional, prognostic, immune and pharmacogenomic profile of ADGRG1/GPR56 across human cancers.Materials and Methods: This in silico pan-cancer study analyzed 10,953 TCGA PanCancer Atlas patients across 32 analytical cohorts for clinical and cBioPortal-based analyses, while GEPIA2 analyses included 33 cancer types, with COAD and READ evaluated separately. ADGRG1/GPR56 expression was evaluated using GEPIA2; overall survival by Kaplan–Meier, log-rank and Cox regression analyses; genomic alterations through cBioPortal; immune infiltration using TIMER3; and drug sensitivity using GDSC and CTRP datasets through GSCA.Results: ADGRG1/GPR56 expression differed significantly between tumor and normal tissues in 16 of 33 cancer types. Nominal Kaplan–Meier analysis showed significant overall survival associations in head and neck squamous cell carcinoma, kidney renal clear cell carcinoma, mesothelioma, skin cutaneous melanoma and uveal melanoma. Among these five cohorts, the association remained significant after BH-FDR correction in continuous Cox analysis for all except skin cutaneous melanoma. Genomic alterations were rare, occurring in approximately 1% of cases, without recurrent mutational hotspots. Immune analyses showed tumor-specific associations with CD4+ T-cell, CD8+ T-cell and macrophage-related signatures. Pharmacogenomic analyses showed mainly resistance-like correlations with cytotoxic and mitotic agents in CTRP and selected epigenetic and PI3K/mTOR-related agents in GDSC, whereas EGFR/ERBB and MEK/MAPK inhibitors showed sensitivity-like correlations.Conclusion: ADGRG1/GPR56 shows a context-dependent profile across human cancers, with clinical relevance linked mainly to tumor-specific expression, immune microenvironmental state and pharmacogenomic patterns rather than recurrent genomic alterations.