Clinical Department of Integrated Traditional Chinese and Western Medicine, The First Clinical Medical College of Shandong University of Traditional Chinese Medicine, Jinan, China.
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Shandong University of Chinese Medicine, Jinan, China.
Front Immunol. 2023 Nov 14;14:1268141. doi: 10.3389/fimmu.2023.1268141. eCollection 2023.
Cuproptosis, the most recently identified and regulated cell death, depends on copper ions . Copper regulates the pathogenesis of Idiopathic pulmonary fibrosis (IPF), but the mechanism of action underlying cuproptosis in IPF remains unclear.
We identified three cuproptosis patterns based on ten cuproptosis-related genes using unsupervised consensus clustering. We quantified these patterns using a PCA algorithm to construct a cuproptosis score. ssGSEA and the Cibersort algorithm assessed the immune profile of IPF patients. GSEA and GSVA were used to analyze the functional differences in different molecular patterns. Drug susceptibility prediction based on cuproptosis scores and meaningful gene markers was eventually screened in combination with external public data sets, experiments and our cases.
Of the three types of cuproptosis-related clusters identified in the study, patients in the clusterA, geneclusterB, and score-high groups showed improved prognoses. Moreover, each cluster exhibited differential immune characteristics, with the subtype showing a poorer prognosis associated with an immune overreaction. Cuproptosis score can be an independent risk factor for predicting the prognosis of IPF patients. GSEA showed a significant functional correlation between the score and cuproptosis. The genes , and , were identified as prognostic-related signatures in IPF patients. The functional role of immune regulation in IPF was further explored by correlating essential genes with immune factors. Also, the nomogram constructed by cumulative information from gene markers and cuproptosis score showed reliable clinical application.
Cuproptosis patterns differ significantly in the prognosis and immune characteristics of IPF patients. The cuproptosis score and five gene signatures can provide a reliable reference in the prognosis and diagnosis of IPF.
铜死亡是最近发现和调控的细胞死亡方式，依赖于铜离子。铜调节特发性肺纤维化（IPF）的发病机制，但 IPF 中铜死亡的作用机制尚不清楚。
我们使用无监督共识聚类基于十个铜死亡相关基因识别了三种铜死亡模式。我们使用 PCA 算法对这些模式进行量化，构建铜死亡评分。ssGSEA 和 Cibersort 算法评估 IPF 患者的免疫特征。GSEA 和 GSVA 用于分析不同分子模式的功能差异。最终结合外部公共数据集、实验和我们的病例，基于铜死亡评分和有意义的基因标志物筛选药物敏感性预测。
在本研究中鉴定的三种铜死亡相关聚类中，clusterA、geneclusterB 和 score-high 组的患者预后较好。此外，每个聚类都表现出不同的免疫特征，亚型表现出较差的预后，与免疫过度反应有关。铜死亡评分可以作为预测 IPF 患者预后的独立危险因素。GSEA 显示评分与铜死亡之间存在显著的功能相关性。基因、和被确定为 IPF 患者的预后相关特征。通过将必需基因与免疫因子相关联，进一步探讨了免疫调节在 IPF 中的功能作用。此外，由基因标志物和铜死亡评分的累积信息构建的列线图显示了可靠的临床应用。
铜死亡模式在 IPF 患者的预后和免疫特征方面存在显著差异。铜死亡评分和五个基因特征可以为 IPF 的预后和诊断提供可靠的参考。
