Wangbing Hong ¹ Xin Wang ² Xinyu Huang ³ Pengfei Chen ^1* Yifan Liu ^1* Ziying zheng ^1* Yinghua Chen ^1* Zengxin Xie ^1* Gongnan Zhan ^1* Xin You ^1* Heping Huang ^1*

• ¹ Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi Province, China
• ² Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, 330006 Jiangxi, China, Nanchang, China
• ³ Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

Melanoma (MM) is the deadliest skin cancer originating from melanocytes. Despite advancements in immunotherapy that have somewhat improved MM prognosis, high levels of resistance continue to result in poor outcomes. In this study, we analyzed the expression patterns and potential mechanisms of WNT signaling pathway genes in MM. Using Cox regression, we identified 19 prognostic-related genes and performed consistency clustering to explore the potential of WNT pathway genes as classifiers for prognosis. We further refined these genes using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to construct a 13-gene prognostic model.This model demonstrated excellent predictive performance and validation at multiple time points. We found that CSNK1E and RAC3 were significantly positively correlated with the epithelial-to-mesenchymal transition (EMT) process, with CSNK1E exhibiting a similar expression trend to EMT-related genes. Additionally, these two genes were negatively correlated with multiple immune cell types and immune checkpoint genes. Pan-cancer analysis revealed the heterogeneous expression and prognostic potential of CSNK1E across various cancers. Wet experiments confirmed that CSNK1E promotes MM proliferation, invasion, and migration, and enhances malignant progression through the TGF-β pathway. These findings highlight the potential of CSNK1E as therapeutic targets in MM, and suggest that the WNT and TGF-β pathways have a synergistic role in the EMT process.