He Shiyue, Peng Wenzhong, Hu Xinyue, Chen Yong
Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.
Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China.
Sci Rep. 2025 Jul 23;15(1):26845. doi: 10.1038/s41598-025-11151-2.
Cuproptosis, a copper-dependent distinct form of cell death, holds a critical role in tumor development. However, further investigation is needed to elucidate the impact of the cuproptosis signaling on thyroid cancer. In this study, comprehensive bioinformatics analyses with six independent cohorts and in vitro experiments were performed to explore the expression, prognostic significance, and molecular function of the cuproptosis key regulator FDX1 in papillary thyroid carcinoma (PTC). LASSO regression analyses were utilized to screen the optimal combination of cuproptosis-related genes for constructing a Cox proportional-hazards model, and the cuproptosis-related risk score (CRRS) was calculated to stratify PTC patients in prognosis. The algorithm of ESTIMATE and ssGSEA were used to investigate the tumor immune microenvironment. Our results showed FDX1 was significantly downregulated in PTC, and its lower expression was closely associated with tumor recurrence. Based on six selected cuproptosis-related genes a predictive prognosis model was established and CRRS displayed a good prediction accuracy. Overexpression of FDX1 could promote cell death and inhibit the viability of tumor cells. Additionally, CYCS played a hub role in the cuproptosis regulatory network and could be upregulated with the overexpression of FDX1. Our study suggests that CRRS can serve as a good prognosis indicator and may provide new insights into cuproptosis-targeted therapies in PTC.
铜死亡是一种依赖铜的独特细胞死亡形式，在肿瘤发展中起着关键作用。然而，需要进一步研究以阐明铜死亡信号传导对甲状腺癌的影响。在本研究中，我们进行了六项独立队列的综合生物信息学分析和体外实验，以探究铜死亡关键调节因子FDX1在甲状腺乳头状癌（PTC）中的表达、预后意义和分子功能。利用LASSO回归分析筛选铜死亡相关基因的最佳组合以构建Cox比例风险模型，并计算铜死亡相关风险评分（CRRS）对PTC患者进行预后分层。运用ESTIMATE和ssGSEA算法研究肿瘤免疫微环境。我们的结果显示，FDX1在PTC中显著下调，其低表达与肿瘤复发密切相关。基于六个选定的铜死亡相关基因建立了预测预后模型，CRRS显示出良好的预测准确性。FDX1的过表达可促进细胞死亡并抑制肿瘤细胞活力。此外，CYCS在铜死亡调节网络中起核心作用，并且可随FDX1的过表达而上调。我们的研究表明，CRRS可作为良好的预后指标，并可能为PTC中针对铜死亡的治疗提供新的见解。
