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铜死亡可预测肺腺癌的风险和临床结局。

Cuproptosis predicts the risk and clinical outcomes of lung adenocarcinoma.

作者信息

Hu Qin, Wang Runtian, Ma Huiyun, Zhang Zhouwei, Xue Qun

机构信息

Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Medical School of Nantong University, Nantong University, Nantong, China.

出版信息

Front Oncol. 2022 Aug 8;12:922332. doi: 10.3389/fonc.2022.922332. eCollection 2022.


DOI:10.3389/fonc.2022.922332
PMID:36003780
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9393616/
Abstract

Copper is an essential microelement for the body and a necessary coregulator for enzymatic reactions, yet an unbalanced copper level promotes reactive oxidation and cytotoxicity, which ultimately induces cell death. Several small molecules targeting copper-induced cell death have been investigated, yet few showed promising therapeutic effects in clinical trials. In March 2022, first introduced the concept and mechanisms of cuproptosis, suggesting that copper-induced cell death targets the tricarboxylic acid (TCA) cycle protein lipoylation. Does this novel form of cell death take part in tumorigenesis or tumor progression? Is cuproptosis related to clinical outcomes of diseases? Is there a cuproptosis-related panel for clinical practice in cancer treatment? Herein, based on 942 samples of lung adenocarcinoma (LUAD), we analyzed on gene set level the existence and predictive value of cuproptosis in disease diagnosis and treatment. We screened out and identified the "cupLA" panel which indicates the risk of LUAD occurrence, clinicopathological features of LUAD patients, and could guide clinicians to refine LUAD subtypes and make treatment choices.

摘要

铜是人体必需的微量元素,也是酶促反应的必要协同调节因子,但铜水平失衡会促进活性氧化和细胞毒性,最终导致细胞死亡。已经研究了几种针对铜诱导细胞死亡的小分子,但在临床试验中很少有显示出有前景的治疗效果。2022年3月,首次提出了铜死亡的概念和机制,表明铜诱导的细胞死亡靶向三羧酸(TCA)循环蛋白脂酰化。这种新型细胞死亡形式是否参与肿瘤发生或肿瘤进展?铜死亡与疾病的临床结局有关吗?在癌症治疗的临床实践中是否存在与铜死亡相关的指标?在此,基于942例肺腺癌(LUAD)样本,我们在基因集水平上分析了铜死亡在疾病诊断和治疗中的存在情况及预测价值。我们筛选并鉴定出了“cupLA”指标,其可指示LUAD发生风险、LUAD患者的临床病理特征,并能指导临床医生细化LUAD亚型并做出治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/7e56abb02206/fonc-12-922332-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/3707d056d1fd/fonc-12-922332-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/54dc294c833d/fonc-12-922332-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/d1eb11c16b48/fonc-12-922332-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/554322bfdaac/fonc-12-922332-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/bcd1f5b12577/fonc-12-922332-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/7e56abb02206/fonc-12-922332-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/3707d056d1fd/fonc-12-922332-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/54dc294c833d/fonc-12-922332-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/d1eb11c16b48/fonc-12-922332-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/554322bfdaac/fonc-12-922332-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/bcd1f5b12577/fonc-12-922332-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca7f/9393616/7e56abb02206/fonc-12-922332-g006.jpg

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[1]
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[6]
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引用本文的文献

[1]
LncRNA PVT1 promotes cuproptosis through transcriptional activation of FDX1 in colorectal cancer.

Redox Biol. 2025-6-7

[2]
Targeting cuproptosis for cancer therapy: Focus on the anti-tumor immune system.

Cancer Pathog Ther. 2024-7-27

[3]
Understanding the relationship between cuproptosis and the development of hepatocellular carcinoma: implications for targeted therapies.

Front Immunol. 2025-3-12

[4]
Lidocaine could promote the cuproptosis through up-regulating the long noncoding RNA DNMBP-AS1 in Hep-2 cells.

BMC Cancer. 2025-1-22

[5]
Involvement of copper in cell death and cancer.

Apoptosis. 2025-2

[6]
Cuproptosis: a promising new target for breast cancer therapy.

Cancer Cell Int. 2024-12-19

[7]
Construction of a prognostic model based on cuproptosis-related genes and exploration of the value of DLAT and DLST in the metastasis for non-small cell lung cancer.

Medicine (Baltimore). 2024-12-6

[8]
Comprehensive Analysis of Characteristics of Cuproptosis-Related LncRNAs Associated with Prognosis of Lung Adenocarcinoma and Tumor Immune Microenvironment.

Pharmaceuticals (Basel). 2024-9-21

[9]
Curcumin suppresses copper accumulation in non-small cell lung cancer by binding ATOX1.

BMC Pharmacol Toxicol. 2024-8-21

[10]
Cuproptosis, the novel type of oxidation-induced cell death in thoracic cancers: can it enhance the success of immunotherapy?

Cell Commun Signal. 2024-7-27

本文引用的文献

[1]
Compartmentalized metabolism supports midgestation mammalian development.

Nature. 2022-4

[2]
Cuproptosis: a copper-triggered modality of mitochondrial cell death.

Cell Res. 2022-5

[3]
Copper induces cell death by targeting lipoylated TCA cycle proteins.

Science. 2022-3-18

[4]
Copper-induced tumor cell death mechanisms and antitumor theragnostic applications of copper complexes.

Nanomedicine (Lond). 2022-2

[5]
Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring.

Mol Cancer. 2022-1-20

[6]
Connecting copper and cancer: from transition metal signalling to metalloplasia.

Nat Rev Cancer. 2022-2

[7]
FDX1 can Impact the Prognosis and Mediate the Metabolism of Lung Adenocarcinoma.

Front Pharmacol. 2021-10-8

[8]
Overcoming the compensatory elevation of NRF2 renders hepatocellular carcinoma cells more vulnerable to disulfiram/copper-induced ferroptosis.

Redox Biol. 2021-10

[9]
Elesclomol induces copper-dependent ferroptosis in colorectal cancer cells via degradation of ATP7A.

Mol Oncol. 2021-12

[10]
High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types.

Ann Oncol. 2021-5

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