Wang Quan, Duan Yinghui, Xu Yu, Li Hao, Yang Yi
Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
The Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China.
NPJ Parkinsons Dis. 2025 Apr 13;11(1):74. doi: 10.1038/s41531-025-00928-x.
Patients with Parkinson's disease (PD) exhibit an increased risk of melanoma, implying shared yet incompletely understood molecular mechanisms. This study aimed to delineate these common and distinct pathways by analyzing gene expression profiles from the Gene Expression Omnibus. A total of 90 differentially expressed genes (DEGs) were commonly regulated, while 173 DEGs exhibited divergent regulation between PD and melanoma. Protein-protein interaction analysis identified SNCA as a central node within a 21-protein network. LASSO regression revealed 13 hub genes (e.g., CCNB1, CCNH, CORO1C, and GSN) with high diagnostic accuracy (AUC >0.93) across both conditions. Gene set enrichment analysis implicated copper-induced cell death (cuproptosis) in PD neurons and melanoma cells, linking this process to hub genes. RT-qPCR confirmed increased SNCA expression during cuproptosis. Additional analyses identified macrophage involvement and WNT-β-catenin signaling as relevant. These findings suggest cuproptosis as a potential therapeutic target in PD and melanoma.
帕金森病（PD）患者患黑色素瘤的风险增加，这意味着存在尚未完全理解的共同分子机制。本研究旨在通过分析基因表达综合数据库中的基因表达谱来描绘这些共同和不同的途径。共有90个差异表达基因（DEG）受到共同调控，而173个DEG在PD和黑色素瘤之间表现出不同的调控。蛋白质-蛋白质相互作用分析确定α-突触核蛋白（SNCA）是一个21蛋白网络中的中心节点。套索回归揭示了13个中心基因（如细胞周期蛋白B1（CCNB1）、细胞周期蛋白H（CCNH）、肌动蛋白结合蛋白1C（CORO1C）和凝溶胶蛋白（GSN））在两种情况下均具有较高的诊断准确性（曲线下面积>0.93）。基因集富集分析表明，铜诱导的细胞死亡（铜死亡）在PD神经元和黑色素瘤细胞中起作用，并将这一过程与中心基因联系起来。逆转录定量聚合酶链反应（RT-qPCR）证实铜死亡期间SNCA表达增加。进一步分析确定巨噬细胞参与和WNT-β-连环蛋白信号传导与之相关。这些发现表明铜死亡可能是PD和黑色素瘤的潜在治疗靶点。
