CSDE1 Intracellular Distribution as a Biomarker of Melanoma Prognosis.

RNA-binding proteins are emerging as critical modulators of oncogenic cell transformation, malignancy and therapy resistance. We have previously found that the RNA-binding protein Cold Shock Domain containing protein E1 (CSDE1) promotes invasion and metastasis of melanoma, the deadliest form of skin cancer and also a highly heterogeneous disease in need of predictive biomarkers and druggable targets. Here, we design a monoclonal antibody useful for IHC in the clinical setting and use it to evaluate the prognosis potential of CSDE1 in an exploratory cohort of 149 whole tissue sections including benign nevi and primary tumors and metastasis from melanoma patients. Contrary to expectations for an oncoprotein, we observed a global decrease in CSDE1 levels with increasing malignancy. However, the CSDE1 cytoplasmic/nuclear ratio exhibited a positive correlation with adverse clinical features of primary tumors and emerged as a robust indicator of progression free survival in cutaneous melanoma, highlighting the potential of CSDE1 as a biomarker of prognosis. Our findings provide a novel feature for prognosis assessment and highlight the intricacies of RNA-binding protein dynamics in cancer progression.

CSDE1: a versatile regulator of gene expression in cancer.

RNA-binding proteins (RBPs) have garnered significant attention in the field of cancer due to their ability to modulate diverse tumor traits. Once considered untargetable, RBPs have sparked renewed interest in drug development, particularly in the context of RNA-binding modulators of translation. This review focuses on one such modulator, the protein CSDE1, and its pivotal role in regulating cancer hallmarks. We discuss context-specific functions of CSDE1 in tumor development, its mechanisms of action, and highlight features that support its role as a molecular adaptor. Additionally, we discuss the regulation of CSDE1 itself and its potential value as biomarker and therapeutic target.