Comprehensive multi-omics pan-cancer analysis revealed that ANTXR1 is a potential biomarker for diagnosis and immunotherapy.

BACKGROUND

Anthrax toxin receptor 1 (ANTXR1, TEM8) has been implicated in tumor angiogenesis and progression, yet its pan-cancer immunological role remains incompletely defined.

METHODS

We conducted an integrative pan-cancer analysis using multi-omics and clinical data from TCGA, GTEx, and public databases to evaluate the expression, prognostic and diagnostic value, genomic features, immune associations, and drug sensitivity of ANTXR1. Single-cell and spatial transcriptomic analyses were performed to define its cellular and spatial distribution. Functional roles were validated in gastric cancer (GC) using in vitro and in vivo models.

RESULTS

ANTXR1 was aberrantly expressed across multiple tumor types and significantly associated with tumor stage and unfavorable prognosis, particularly in GC. Diagnostic analyses demonstrated high accuracy of ANTXR1 in several malignancies. Elevated ANTXR1 expression correlated with genomic instability, stromal enrichment, M2 macrophage infiltration, and reduced CD8⁺ T cell abundance, indicating an immunosuppressive tumor microenvironment. Single-cell and spatial analyses identified fibroblasts as the primary source of ANTXR1 with co-localization to extracellular matrix components. Functionally, ANTXR1 knockdown suppressed GC cells proliferation, migration, invasion, and tumor growth, inhibited M2 macrophage polarization, and enhanced CD8⁺ T cell activity, partly through PI3K/AKT pathway inhibition.

CONCLUSION

ANTXR1 functions as a stromal-associated immunomodulatory driver of tumor progression and immune suppression, representing a promising biomarker and therapeutic target in stromal-rich cancers.