Globo-H diagnostic stratification and identification of DUSP14 as a candidate target in colorectal cancer.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, underscoring the urgent need for precise and personalized therapeutic strategies. Globo-H has emerged as a clinically relevant glycan target with promising diagnostic and therapeutic utility across multiple cancer types. In this study, we stratified colorectal cancer patients into Globo-H-high and Globo-H-low groups using a histology-based classification, followed by RNA-sequencing analyses to elucidate the key signaling pathways associated with Globo-H overactivation. Among the 31 genes that were identified to meet the Globo-H histology criterion, DUSP14 (dual specificity phosphatase 14) emerged as a promising pharmacological target associated with Globo-H abundance. DUSP14 is an underexplored but pharmacologically actionable therapeutic target. DUSP14 protein in colon cancer cells is inversely correlated with total Transforming growth factor-β-activated kinase 1 (TAK1) protein. The druggability of DUSP14 was demonstrated through in vitro using cell lines and patient-derived organoids (PDO). These results enhance current diagnostic frameworks and provide a foundation for developing novel targeted therapies. Further, in vivo studies are warranted to evaluate the potential of Globo-H targeting in combination with standard treatment regimens. Overall, our work highlights the value of integrating PDO-based functional assays with molecular profiling to uncover and validate actionable targets for CRC theranostics.