Hong Wangbing, Wang Xin, Huang Xinyu, Chen Pengfei, Liu Yifan, Zheng Ziying, You Xin, Chen Yinghua, Xie Zengxin, Zhan Gongnan, Huang Heping
Department of Plastic and Cosmetic Surgery, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China.
Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Front Pharmacol. 2025 Jan 13;15:1501849. doi: 10.3389/fphar.2024.1501849. eCollection 2024.
Melanoma (MM), the deadliest form of skin cancer, originates from melanocytes. Despite advances in immunotherapy that have somewhat improved the prognosis for MM patients, high levels of resistance to treatment continue to result in poor clinical outcomes. Identifying novel biomarkers and therapeutic targets is critical for improving the prognosis and treatment of MM.
In this study, we analyzed the expression patterns of WNT signaling pathway genes in MM and explored their potential mechanisms. Using Cox regression analysis, we identified 19 prognostic-related genes. Consistency clustering was performed to evaluate the potential of these genes as classifiers for prognosis. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was then applied to refine the gene set and construct a 13-gene prognostic model. We validated the model at multiple time points to assess its predictive performance. Additionally, correlation analyses were performed to investigate the relationships between key genes and processes, including epithelial-to-mesenchymal transition (EMT) and immune responses.
We identified that CSNK1E and RAC3 were significantly positively correlated with the EMT process, with CSNK1E showing a similar expression trend to EMT-related genes. Both genes were also negatively correlated with multiple immune cell types and immune checkpoint genes. The 13-gene prognostic model demonstrated excellent predictive performance in MM prognosis. Pan-cancer analysis further revealed heterogeneous expression patterns and prognostic potential of CSNK1E across various cancers. Wet experiments confirmed that CSNK1E promotes MM cell proliferation, invasion, and migration, and enhances malignant progression through the TGF-β signaling pathway.
Our findings suggest that CSNK1E plays a crucial role in MM progression and could serve as a potential therapeutic target. The WNT and TGF-β pathways may work synergistically in regulating the EMT process in MM, highlighting their potential as novel therapeutic targets. These insights may contribute to the development of more effective treatments for MM, particularly for overcoming resistance to current therapies.
黑色素瘤（MM）是皮肤癌中最致命的一种，起源于黑素细胞。尽管免疫疗法取得了进展，在一定程度上改善了MM患者的预后，但高水平的治疗耐药性仍导致临床结果不佳。识别新的生物标志物和治疗靶点对于改善MM的预后和治疗至关重要。
在本研究中，我们分析了MM中WNT信号通路基因的表达模式，并探讨了其潜在机制。使用Cox回归分析，我们鉴定出19个与预后相关的基因。进行一致性聚类以评估这些基因作为预后分类器的潜力。然后应用最小绝对收缩和选择算子（LASSO）算法优化基因集并构建一个13基因的预后模型。我们在多个时间点验证该模型以评估其预测性能。此外，进行相关性分析以研究关键基因与过程之间的关系，包括上皮-间质转化（EMT）和免疫反应。
我们发现CSNK1E和RAC3与EMT过程显著正相关，CSNK1E显示出与EMT相关基因相似的表达趋势。这两个基因也与多种免疫细胞类型和免疫检查点基因呈负相关。13基因预后模型在MM预后中表现出优异的预测性能。泛癌分析进一步揭示了CSNK1E在各种癌症中的异质表达模式和预后潜力。湿实验证实CSNK1E促进MM细胞增殖、侵袭和迁移，并通过TGF-β信号通路增强恶性进展。
我们的研究结果表明CSNK1E在MM进展中起关键作用，可作为潜在的治疗靶点。WNT和TGF-β通路可能在调节MM的EMT过程中协同作用，突出了它们作为新治疗靶点的潜力。这些见解可能有助于开发更有效的MM治疗方法，特别是用于克服对当前疗法的耐药性。
