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用于预测肝细胞癌预后的新型铜死亡与免疫相关特征的开发与验证

Development and Validation of the novel Cuproptosis- and Immune-related Signature for Predicting Prognosis in Hepatocellular Carcinoma.

作者信息

Zhang Yongping, Sui Ping, Zhong Cheng, Liu Jiansheng

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.

Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, China.

出版信息

J Cancer. 2024 Feb 25;15(8):2260-2275. doi: 10.7150/jca.92558. eCollection 2024.

DOI:10.7150/jca.92558
PMID:38495502
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10937287/
Abstract

: Hepatocellular carcinoma often results in late-stage diagnosis, leading to decreased treatment success. To improve prognosis, this study integrates cuproptosis with immune risk scoring models for HCC patients. We identified differentially expressed genes connected to cuproptosis and immune responses using Pearson correlation. A risk signature was then constructed via LASSO regression, and its robustness was validated in the International Cancer Genome Consortium dataset. Additionally, qPCR confirmed findings in tumor and normal tissues. : Eight genes emerged as key prognostic markers from the 110 differentially expressed genes linked to cuproptosis and immunity. A risk-scoring model was developed using gene expression, effectively categorizing patients into low- or high-risk groups. Validated in the ICGC dataset, high-risk patients had significantly reduced survival times. Multivariate Cox regression affirmed the risk signature's independent predictive capability. A clinical nomogram based on the risk signature was generated. Notably, low-risk patients might benefit more from immune checkpoint inhibitors. qPCR and western blotting results substantiated our bioinformatics findings. : The genetic risk signature linked to cuproptosis and immunity holds potential as a vital prognostic biomarker for Hepatocellular carcinoma, providing avenues for tailored therapeutic strategies.

摘要

肝细胞癌常导致晚期诊断,从而降低治疗成功率。为改善预后,本研究将铜死亡与肝癌患者的免疫风险评分模型相结合。我们使用Pearson相关性分析确定了与铜死亡和免疫反应相关的差异表达基因。然后通过LASSO回归构建风险特征,并在国际癌症基因组联盟数据集中验证其稳健性。此外,qPCR在肿瘤组织和正常组织中证实了研究结果。:在与铜死亡和免疫相关的110个差异表达基因中,有8个基因成为关键的预后标志物。利用基因表达建立了风险评分模型,有效地将患者分为低风险组或高风险组。在ICGC数据集中得到验证,高风险患者的生存时间显著缩短。多变量Cox回归证实了风险特征的独立预测能力。生成了基于风险特征的临床列线图。值得注意的是,低风险患者可能从免疫检查点抑制剂中获益更多。qPCR和蛋白质印迹结果证实了我们的生物信息学研究结果。:与铜死亡和免疫相关的遗传风险特征有望成为肝细胞癌重要的预后生物标志物,为量身定制治疗策略提供途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/10937287/5d0766efbf1e/jcav15p2260g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7620/10937287/5d0766efbf1e/jcav15p2260g009.jpg

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本文引用的文献

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Identification of the cuproptosis-related molecular subtypes and an immunotherapy prognostic model in hepatocellular carcinoma.鉴定肝细胞癌中与铜死亡相关的分子亚型和免疫治疗预后模型。
BMC Bioinformatics. 2022 Nov 16;23(1):485. doi: 10.1186/s12859-022-04997-0.
2
Cuproptosis regulator-mediated patterns associated with immune infiltration features and construction of cuproptosis-related signatures to guide immunotherapy.铜死亡调控因子相关模式与免疫浸润特征相关,并构建铜死亡相关特征以指导免疫治疗。
Front Immunol. 2022 Sep 29;13:945516. doi: 10.3389/fimmu.2022.945516. eCollection 2022.
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TMEM164 is a new determinant of autophagy-dependent ferroptosis.
TMEM164 是自噬依赖性铁死亡的一个新决定因素。
Autophagy. 2023 Mar;19(3):945-956. doi: 10.1080/15548627.2022.2111635. Epub 2022 Aug 22.
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Cuproptosis-Related Risk Score Predicts Prognosis and Characterizes the Tumor Microenvironment in Hepatocellular Carcinoma.铜死亡相关风险评分预测肝细胞癌的预后并描绘肿瘤微环境。
Front Immunol. 2022 Jul 11;13:925618. doi: 10.3389/fimmu.2022.925618. eCollection 2022.
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Cell division cycle associated 2 (CDCA2) upregulation promotes the progression of hepatocellular carcinoma in a p53-dependant manner.细胞分裂周期相关蛋白 2(CDCA2)上调以依赖 p53 的方式促进肝细胞癌的进展。
PeerJ. 2022 Jun 6;10:e13535. doi: 10.7717/peerj.13535. eCollection 2022.
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A Novel Cuproptosis-Related Prognostic Gene Signature and Validation of Differential Expression in Clear Cell Renal Cell Carcinoma.一个新的铜死亡相关预后基因特征,并在透明细胞肾细胞癌中验证差异表达。
Genes (Basel). 2022 May 10;13(5):851. doi: 10.3390/genes13050851.
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Cuproptosis: a new form of programmed cell death.铜死亡:一种新的程序性细胞死亡形式。
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Transmembrane Protein-Based Risk Model and H3K4me3 Modification Characteristics in Lung Adenocarcinoma.基于跨膜蛋白的肺腺癌风险模型及H3K4me3修饰特征
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