Pan-cancer multi-omic integration of Trop2 reveals biological determinants and translational implications for ADC therapy

Abstract Trop2–directed antibody-drug conjugates (ADCs) show activity across epithelial cancers, yet determinants of target expression in tumors and normal tissues remain poorly defined. We integrated bulk and single-cell transcriptomic profiles from over 20,000 samples across TCGA, GTEx and public atlases to map TACSTD2 expression, regulation and functional correlates in solid malignancies and healthy epithelia. TACSTD2 was restricted to epithelial lineages, enriched in multiple tumors and detectable in selected normal epithelia. Genomic alterations were uncommon, whereas DNA methylation showed a consistent