PDF(Pubmed)
Abstract：
UNASSIGNED: Abnormal accumulation of copper could induce cell death and tumor growth, and affect tumor immune escape by regulating programmed cell death ligand 1 (PD-L1) expression. This study aims to establish and verify a risk signature based on cuproptosis- and immune-related genes (CIRGs) for hepatocellular carcinoma (HCC) management.
UNASSIGNED: HCC RNA-seq and clinical data were obtained from open databases. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were utilized to screen CIRGs and develop a risk signature. The signature\'s value for clinical applications, functional enrichment, tumor mutation burden (TMB), and immune profile analyses were investigated systematically.
UNASSIGNED: A risk signature was developed utilizing seven CIRGs, and it performed well in predicting the prognosis of HCC patients in both the training and external validation cohorts. The model\'s risk score was discovered to be related to important clinical features. Top 15 mutated genes in HCC were significantly different among different risk groups. High-risk patients showed higher TMB, and high TMB was closely identified with a poorer prognosis. Immune profile analyses showed that immune infiltration level was higher in low-risk patients than high-risk patients, and the level of immune checkpoint genes expression varied significantly between patients in two different risk groups. Low-risk patients responded well to immunotherapy treatment, whereas high-risk patients were more sensitive to sorafenib, doxorubicin, gemcitabine and AKT (also known as protein kinase B) inhibitors.
UNASSIGNED: The established risk signature based on CIRGs can not only well predict the prognosis of HCC patients but is also promising in evaluating TMB and treatment response to immunotherapy, targeted therapy and chemotherapy, which has the potential to assist in the clinical management of HCC.
UNASSIGNED: HCC RNA-seq and clinical data were obtained from open databases. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were utilized to screen CIRGs and develop a risk signature. The signature\'s value for clinical applications, functional enrichment, tumor mutation burden (TMB), and immune profile analyses were investigated systematically.
UNASSIGNED: A risk signature was developed utilizing seven CIRGs, and it performed well in predicting the prognosis of HCC patients in both the training and external validation cohorts. The model\'s risk score was discovered to be related to important clinical features. Top 15 mutated genes in HCC were significantly different among different risk groups. High-risk patients showed higher TMB, and high TMB was closely identified with a poorer prognosis. Immune profile analyses showed that immune infiltration level was higher in low-risk patients than high-risk patients, and the level of immune checkpoint genes expression varied significantly between patients in two different risk groups. Low-risk patients responded well to immunotherapy treatment, whereas high-risk patients were more sensitive to sorafenib, doxorubicin, gemcitabine and AKT (also known as protein kinase B) inhibitors.
UNASSIGNED: The established risk signature based on CIRGs can not only well predict the prognosis of HCC patients but is also promising in evaluating TMB and treatment response to immunotherapy, targeted therapy and chemotherapy, which has the potential to assist in the clinical management of HCC.
摘要：
■铜的异常积累可以诱导细胞死亡和肿瘤生长，并通过调节程序性细胞死亡配体1(PD-L1)表达影响肿瘤免疫逃逸。本研究旨在建立和验证基于巯基和免疫相关基因（CIRGs）的肝细胞癌（HCC）管理的风险特征。
■HCCRNA-seq和临床数据来自开放数据库。利用最小绝对收缩和选择算子（LASSO）和Cox回归分析筛选CIRGs并开发风险特征。签名对临床应用的价值，功能富集，肿瘤突变负荷（TMB），和免疫谱分析进行了系统研究。
■利用七个CIRGs开发了风险签名，在训练和外部验证队列中，它在预测HCC患者的预后方面表现良好。发现模型的风险评分与重要的临床特征有关。HCC中的前15个突变基因在不同风险组之间存在显着差异。高危患者表现出更高的TMB，高TMB与预后较差密切相关。免疫谱分析显示,低危患者的免疫浸润水平高于高危患者,免疫检查点基因表达水平在两个不同风险组的患者之间差异显著。低风险患者对免疫治疗反应良好，而高危患者对索拉非尼更敏感，阿霉素,吉西他滨和AKT（也称为蛋白激酶B）抑制剂。
■建立的基于CIRGs的风险特征不仅可以很好地预测HCC患者的预后，而且在评估TMB和免疫治疗的治疗反应方面也很有希望。靶向治疗和化疗，这有可能协助肝癌的临床管理。
■HCCRNA-seq和临床数据来自开放数据库。利用最小绝对收缩和选择算子（LASSO）和Cox回归分析筛选CIRGs并开发风险特征。签名对临床应用的价值，功能富集，肿瘤突变负荷（TMB），和免疫谱分析进行了系统研究。
■利用七个CIRGs开发了风险签名，在训练和外部验证队列中，它在预测HCC患者的预后方面表现良好。发现模型的风险评分与重要的临床特征有关。HCC中的前15个突变基因在不同风险组之间存在显着差异。高危患者表现出更高的TMB，高TMB与预后较差密切相关。免疫谱分析显示,低危患者的免疫浸润水平高于高危患者,免疫检查点基因表达水平在两个不同风险组的患者之间差异显著。低风险患者对免疫治疗反应良好，而高危患者对索拉非尼更敏感，阿霉素,吉西他滨和AKT（也称为蛋白激酶B）抑制剂。
■建立的基于CIRGs的风险特征不仅可以很好地预测HCC患者的预后，而且在评估TMB和免疫治疗的治疗反应方面也很有希望。靶向治疗和化疗，这有可能协助肝癌的临床管理。
