CEACAM1 Is Associated With an Immune-Activated Tumor Microenvironment and Therapeutic Stratification in Sarcoma

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional immunomodulatory protein involved in both immune activation and immune suppression across diverse cancer types. However, its biological significance and clinical relevance in sarcoma (SARC) remain poorly defined. A comprehensive multiomics analysis of CEACAM1 was performed by integrating transcriptomic, genomic, epigenetic, immunological, and pharmacogenomic data from TCGA, GTEx, CPTAC, and large-scale drug sensitivity datasets. CEACAM1 expression patterns, prognostic value, immune infiltration characteristics, pathway associations, genomic alterations, DNA methylation, transcriptional regulation, and therapeutic response were systematically evaluated. In SARC, elevated CEACAM1 expression was significantly associated with favorable clinical outcomes and characterized by an immune-enriched tumor microenvironment. High CEACAM1 expression correlated with increased CD8⁺ T-cell infiltration, enhanced interferon-γ signaling, enrichment of tertiary lymphoid structure signatures, and upregulation of immune effector genes. Functional enrichment analyses further linked CEACAM1 to immune-related pathways, including inflammatory response, interferon signaling, and apoptosis. At the therapeutic level, CEACAM1 expression was associated with reduced sensitivity to multiple chemotherapeutic agents, while concurrently correlating with enrichment of immunotherapy-responsive gene signatures, indicating a distinct immune-active yet therapeutically heterogeneous subtype of SARC. Collectively, these findings suggest that CEACAM1 represents a potential biomarker of immune activation and therapeutic stratification in SARC, warranting further investigation as a predictive indicator and immunotherapy-related target in mesenchymal malignancies.