Aberrant Expression of CYP2W1 in Pediatric Soft Tissue Sarcomas: Clinical Significance and Potential as a Therapeutic Target.

Abstract

Pediatric soft-tissue sarcomas (STSs) are aggressive malignancies with poor prognoses, particularly in recurrent and metastatic cases. Standard therapies, such as cytotoxic chemotherapy, offer limited survival benefits and carry significant toxicities, underscoring the urgent need for innovative therapeutic approaches. CYP2W1, a tumor-specific monooxygenase enzyme, has emerged as a promising therapeutic target due to its aberrant expression in various cancers. However, its role in pediatric STSs remains poorly understood. This study evaluated CYP2W1 expression in 42 pediatric STS samples across seven histological subtypes using qPCR and Western blot analyses. High CYP2W1 expression was detected in 69% of tumor samples at the mRNA level and in 40.5% at the protein level, compared to absent or negligible expression in matched normal tissues (p < 0.001). Synovial sarcoma and rhabdomyosarcoma subtypes exhibited the highest CYP2W1 protein expression, at 70% and 62.5%, respectively. Furthermore, CYP2W1 expression was significantly associated with higher histological grade, advanced tumor stage, and a trend toward reduced overall survival (p = 0.082). These findings indicate that CYP2W1 is aberrantly expressed in a subset of pediatric STSs, contributing to tumor aggressiveness and highlighting its potential as a novel therapeutic target for these challenging malignancies.