ADAMDEC1 predicts prognosis and immunotherapy response in a pan-cancer study with experimental validation

ADAMDEC1 (a disintegrin and metalloproteinase domain-like protein decysin-1) is linked to immune disorders and cancers, but its pan-cancer role remains unclear. We analyzed ADAMDEC1 using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) for expression, prognosis, immune infiltration, and therapy response. Single-cell RNA sequencing (scRNA-seq) and genomic alterations were examined. Gene set enrichment analysis (GSEA) assessed pathways. Immunohistochemistry (IHC) validated ADAMDEC1 in esophageal cancer (ESCA) tissue microarray (n = 48). Immunotherapy response was predicted using Tumor Immune Dysfunction and Exclusion (TIDE) and independent cohorts. ADAMDEC1 was dysregulated across cancers with context-dependent prognosis: high expression correlated with poor survival in lower-grade glioma (LGG) and uveal melanoma (UVM), but better outcomes in ovarian cancer (OV) and skin cutaneous melanoma (SKCM). Single-cell analysis revealed a dichotomy: in UVM, ADAMDEC1 was mainly in tumor-associated macrophages; in SKCM, it was broadly expressed across malignant, immune, and stromal cells. DNA methylation inversely correlated with expression in 20 cancers. ADAMDEC1 linked to immune infiltration and immunomodulatory genes including programmed cell death protein 1 (PD-1). In ESCA, ADAMDEC1 was elevated in metastasis and positively correlated with PD-1. ADAMDEC1 predicted immunotherapy response comparably to conventional biomarkers. ADAMDEC1 is a context-dependent immune regulator with prognostic direction determined by cellular origin, supporting its investigation as a therapeutic target and biomarker in precision oncology.