与肝细胞癌患者的预后和免疫治疗相关的铜代谢异常相关预后标志物可预测其预后和免疫治疗效果。
Cuproptosis-related prognostic signatures predict the prognosis and immunotherapy in HCC patients.
发表日期:2023 Aug 25
作者:
Hong Peng, Zhaoxia Zou, Ziye Xiang, Xingjun Lu, Yiya Zhang, Xiaozhen Peng
来源:
Cell Death & Disease
摘要:
铜死亡是一种非常罕见的程序性细胞死亡机制,与特定线粒体代谢酶的紊乱在肿瘤的发生和发展中起着作用。然而,关于铜死亡相关基因(CRGs)如何影响肝细胞性肝癌(HCC)的潜力以及HCC的预后仍然不明确。本研究使用癌症基因组图谱和国际癌症基因组联盟的数据评估了HCC中14个CRGs的情况。然后,筛选出4个CRGs(ATP7A、MTF1、GLS和CDKN2A)用于构建预后和药物治疗的风险标志。CRGs高风险的HCC患者显示较低风险患者预后差。此外,CRGs风险标志被证明是独立的预后因子,与HCC的免疫微环境相关。同时,我们基于铜死相关长非编码RNA(Cr-lncRNAs)构建了一个预测模型并加以验证。我们获得了291个Cr-lncRNAs,并基于3个关键的Cr-lncRNAs(AC026356.1、NRAV、AL031985.3)构建了Cr-lncRNA预测标志。Cr-lncRNA预测标志也是独立的预后因子,并与HCC的免疫微环境相关。最后,药物敏感性数据库显示了与CRGs标志和Cr-lncRNAs标志相关的8个候选药物。总之,我们评估和验证了CRGs和Cr-lncRNAs作为预后、免疫治疗和药物候选的潜在预测标志,为HCC的个体化诊断和治疗提供了依据。版权所有© 2023 作者。Wolters Kluwer Health, Inc.出版。
Cuproptosis, an unusual type of programmed cell death mechanism of cell death, involved the disruption of specific mitochondrial metabolic enzymes in the occurrence and development of tumors. However, it was still unclear how the relationship between cuproptosis-related genes (CRGs) may contribute to hepatocellular carcinoma (HCC) potential the prognosis of HCC remained limited. Here, the landscape of 14 CRGs in HCC was evaluated using the Cancer Genome Atlas and International Cancer Genome Consortium datasets. And then, 4 CRGs (ATP7A, MTF1, GLS, and CDKN2A) were screened for the construction of risk signatures for prognosis and drug therapy. The HCC patients with CRGs high-risk showed poor prognosis than those with low risk. Moreover, the CRGs risk signature was shown to be an independent prognostic factor and associated with the immune microenvironment in HCC. Meanwhile, we constructed and verified a prognostic model based on cuproptosis-related lncRNAs (Cr-lncRNAs). We obtained 291 Cr-lncRNAs and constructed Cr-lncRNA prognosis signature based on 3 key Cr-lncRNAs (AC026356.1, NRAV, AL031985.3). The Cr-lncRNA prognosis signature was also an independent prognostic factor and associated with the immune microenvironment in HCC. Finally, the drug sensitivity database showed that 8 candidate drugs related to CRGs signature and Cr-lncRNAs signature. In summary, we evaluated and validated the CRGs and Cr-lncRNAs as potential predictive markers for prognosis, immunotherapy, and drug candidate with the personalized diagnosis and treatment of HCC.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.