Lv Haozhen, Liu Lin, He Yuexi, Yang Kun, Fu Yu, Bao Yingqiu
Department of Dermatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Peking Union Medical College, Beijing, China.
Front Pharmacol. 2024 Mar 7;15:1344755. doi: 10.3389/fphar.2024.1344755. eCollection 2024.
Melanoma is the most lethal type of skin cancer with an increasing incidence. Cuproptosis is the most recently identified copper-dependent form of cell death that relies on mitochondrial respiration. The hippocampal (Hippo) pathway functions as a tumor suppressor by regulating Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) activity. However, its role in cuproptosis remains unknown. In addition, the correlation of cuproptosis-related genes and Hippo pathway-related genes with tumor prognosis warrants further investigation. In the present study, we explored the correlation of cuproptosis-related genes and Hippo pathway-related genes with the prognosis of melanoma through analysis of data from a public database and experimental verification. We found eight Hippo pathway-related genes that were downregulated in melanoma and exhibited predictive value for prognosis. There was a significant positive correlation between cuproptosis-related genes and Hippo pathway-related genes in skin cutaneous melanoma. YAP1 expression was positively correlated with ferredoxin 1 (FDX1) expression in the GSE68599 dataset and A2058 cells. Moreover, YAP1 was positively and negatively correlated with M2 macrophages and regulatory T cell infiltration, respectively. In conclusion, the present study demonstrated the prognostic value of Hippo pathway-related genes (particularly YAP1) in melanoma, revealing the correlation between the expression of Hippo pathway-related genes and immune infiltration. Thus, the present findings may provide new clues on the prognostic assessment of patients with melanoma and a new target for the immunotherapy of this disease.
黑色素瘤是最致命的皮肤癌类型，其发病率呈上升趋势。铜死亡是最近发现的一种依赖线粒体呼吸的铜依赖性细胞死亡形式。海马（Hippo）通路通过调节Yes相关蛋白/含PDZ结合基序的转录共激活因子（YAP/TAZ）活性发挥肿瘤抑制作用。然而，其在铜死亡中的作用尚不清楚。此外，铜死亡相关基因和Hippo通路相关基因与肿瘤预后的相关性值得进一步研究。在本研究中，我们通过分析公共数据库的数据和实验验证，探讨了铜死亡相关基因和Hippo通路相关基因与黑色素瘤预后的相关性。我们发现8个与Hippo通路相关的基因在黑色素瘤中表达下调，并具有预后预测价值。皮肤黑色素瘤中铜死亡相关基因与Hippo通路相关基因之间存在显著正相关。在GSE68599数据集和A2058细胞中，YAP1表达与铁氧化还原蛋白1（FDX1）表达呈正相关。此外，YAP1分别与M2巨噬细胞和调节性T细胞浸润呈正相关和负相关。总之，本研究证明了Hippo通路相关基因（特别是YAP1）在黑色素瘤中的预后价值，揭示了Hippo通路相关基因表达与免疫浸润之间的相关性。因此，本研究结果可能为黑色素瘤患者的预后评估提供新线索，并为该疾病的免疫治疗提供新靶点。
