CEP55 Promotes Acral Melanoma Progression via MAPK Pathway and Predicts Survival Following Immunotherapy

Acral melanoma (AM) is the predominant subtype of cutaneous melanoma in Asian populations, characterized by more aggressive clinical features and limited neoadjuvant therapy response. Centrosomal protein 55 kDa (CEP55) has been implicated in the pathogenesis of various malignancies, but its role in AM remains undefined.

CEP55 expression in melanoma tissues and cell lines was analyzed by RT-qPCR, Western blotting, and immunohistochemistry (IHC). Databases (GEPIA, Sangerbox, Kaplan-Meier plotter, and TIMER) were used to analyze the expression of CEP55 and its correlation with clinical data of melanoma patients. Functional assays were conducted in vitro and in vivo. RNA sequencing (RNA-seq) and rescue experiments were used to explore underlying mechanisms. Tissue microarrays were used to verify the relationship between CEP55 and immune checkpoints.

CEP55 overexpression is associated with Breslow thickness and TNM stage in melanoma tissues and cell lines. CEP55 knockdown inhibited melanoma cell proliferation, migration, and invasion. And CEP55 activated mitogen-activated protein kinase (MAPK) signaling, leading to BRAF inhibitor resistance. Besides, CEP55 overexpression was associated with more favorable responses to immunotherapy in melanoma patients.

CEP55 plays a critical role in AM progression and immunotherapy. Targeting CEP55 may be a promising therapeutic strategy for AM.