Wu Gujie, Hu Qin, Chen Hongyu, He Min, Ma Huiyun, Zhou Lin, Xu Kun, Ren Hefei, Qi Juntao
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Research Center of Clinical Medicine, Shenzhen Hospital of Shanghai University of Traditional Chinese Medicine, Shenzhen, China.
Front Oncol. 2023 Mar 15;13:1127768. doi: 10.3389/fonc.2023.1127768. eCollection 2023.
Cuproptosis is a novel form of programmed cell death that disrupts the tricarboxylic acid (TCA) cycle and mitochondrial function. The mechanism of cuproptosis is quite different from that of common forms of cell death such as apoptosis, pyroptosis, necroptosis, and ferroptosis. However, the potential connection between cuproptosis and tumor immunity, especially in lung adenocarcinoma (LUAD), is poorly understood.
We used machine learning algorithms to develop a cuproptosis-related scoring system. The immunological features of the scoring system were investigated by exploring its association with clinical outcomes, immune checkpoint expression, and prospective immunotherapy response in LUAD patients. The system predicted the sensitivity to chemotherapeutic agents. Unsupervised consensus clustering was performed to precisely identify the different cuproptosis-based molecular subtypes and to explore the underlying tumor immunity.
We determined the aberrant expression and prognostic relevance of cuproptosis-related genes (CRGs) in LUAD. There were significant differences in survival, biological function, and immune infiltration among the cuproptosis subtypes. In addition, the constructed cuproptosis scoring system could predict clinical outcomes, tumor microenvironment, and efficacy of targeted drugs and immunotherapy in patients with LUAD. After validating with large-scale data, we propose that combining the cuproptosis score and immune checkpoint blockade (ICB) therapy can significantly enhance the efficacy of immunotherapy and guide targeted drug application in patients with LUAD.
The Cuproptosis score is a promising biomarker with high accuracy and specificity for determining LUAD prognosis, molecular subtypes, immune cell infiltration, and treatment options for immunotherapy and targeted therapies for patients with LUAD. It provides novel insights to guide personalized treatment strategies for patients with LUAD.
铜死亡是一种新型程序性细胞死亡形式，它会破坏三羧酸（TCA）循环和线粒体功能。铜死亡的机制与细胞凋亡、焦亡、坏死性凋亡和铁死亡等常见细胞死亡形式有很大不同。然而，铜死亡与肿瘤免疫之间的潜在联系，尤其是在肺腺癌（LUAD）中的联系，目前尚不清楚。
我们使用机器学习算法开发了一个与铜死亡相关的评分系统。通过探索该评分系统与LUAD患者临床结局、免疫检查点表达及前瞻性免疫治疗反应之间的关联，研究其免疫特征。该系统预测了对化疗药物的敏感性。进行无监督一致性聚类以精确识别不同的基于铜死亡的分子亚型，并探索潜在的肿瘤免疫。
我们确定了LUAD中铜死亡相关基因（CRGs）的异常表达及其预后相关性。铜死亡亚型在生存、生物学功能和免疫浸润方面存在显著差异。此外，构建的铜死亡评分系统可以预测LUAD患者的临床结局、肿瘤微环境以及靶向药物和免疫治疗的疗效。在通过大规模数据验证后，我们提出将铜死亡评分与免疫检查点阻断（ICB）治疗相结合可以显著提高免疫治疗的疗效，并指导LUAD患者的靶向药物应用。
铜死亡评分是一种有前景的生物标志物，对于确定LUAD的预后、分子亚型、免疫细胞浸润以及LUAD患者免疫治疗和靶向治疗的治疗选择具有高准确性和特异性。它为指导LUAD患者的个性化治疗策略提供了新的见解。
