Clinical features and molecular landscape of cuproptosis signature‐related molecular subtype in gastric cancer DOI Creative Commons
Wei Chong,

Huicheng Ren,

Hao Chen

et al.

iMeta, Journal Year: 2024, Volume and Issue: 3(3)

Published: April 5, 2024

Abstract Recent studies have highlighted the biological significance of cuproptosis in disease occurrence and development. However, it remains unclear whether signaling also has potential impacts on tumor initiation prognosis gastric cancer (GC). In this study, 16 cuproptosis‐related genes (CRGs) transcriptional profiles were harnessed to perform regularized latent variable model‐based clustering GC. A signature risk scoring (CSRS) scheme, based a weighted sum principle components CRGs, was used evaluate individual tumors Four distinct signature‐based clusters, characterized by differential expression patterns identified among 1136 GC samples across three independent databases. The four clusters associated with different clinical outcomes immune contexture. Based CSRS, patients can be divided into CSRS‐High CSRS‐Low subtypes. We found that DBT, MTF1 , ATP7A significantly elevated subtype, while SLC31A1, GCSH, LIAS, DLAT, FDX1, DLD PDHA1 increased subtype. Patients score prolonged survival time. Further analysis indicated correlated greater mutation burden (TMB) higher rates mutated (SMG) addition, subtype harbored more amplified focal regions related tumorigenesis ( 3q27.1, 12p12.1, 11q13.3 etc.) than tumors. Drug sensitivity analyses revealed compounds for treatment score, which experimentally validated using cells. This study highlights subtyping is features molecular landscape Quantitative evaluation CSRS will strengthen our understanding development progress

Language: Английский

Cuproptosis: mechanisms and links with cancers DOI Creative Commons
Jiaming Xie, Yannan Yang, Yibo Gao

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 7, 2023

Abstract Cuproptosis was a copper-dependent and unique kind of cell death that separate from existing other forms death. The last decade has witnessed considerable increase in investigations programmed death, whether copper induced an independent form long been argued until mechanism cuproptosis revealed. After that, increasing number researchers attempted to identify the relationship between process cancer. Thus, this review, we systematically detailed systemic cellular metabolic processes copper-related tumor signaling pathways. Moreover, not only focus on discovery its mechanism, but also outline association cancers. Finally, further highlight possible therapeutic direction employing ion ionophores with cuproptosis-inducing functions combination small molecule drugs for targeted therapy treat specific

Language: Английский

Citations

398
Regulatory roles of copper metabolism and cuproptosis in human cancers DOI Creative Commons
Zhe Wang,

Dekui Jin,

Shuaishuai Zhou

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: March 23, 2023

Copper is an essential micronutrient for human body and plays a vital role in various biological processes including cellular respiration free radical detoxification. Generally, copper metabolism the stable state, there are specific mechanisms to regulate maintain homeostasis. Dysregulation of may have great connection with types diseases, such as Wilson disease causing overload Menkes deficiency. Cancer presents high mortality rates world due unlimited proliferation potential, apoptosis escape immune properties induce organ failure. thought cancer, elevated levels cancer tissue serum. also affects tumor progression by affecting angiogenesis, metastasis other processes. Notably, cuproptosis novel form cell death that provide targeting strategies developing therapy. chelators ionophores two coordinating compounds treatment cancer. This review will explore relationship between cancers, clarify targeted

Language: Английский

Citations

69
Copper homeostasis and cuproptosis in mitochondria DOI

Ziying Tian,

Su Jiang,

Jieyu Zhou

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 334, P. 122223 - 122223

Published: Oct. 29, 2023

Language: Английский

Citations

42
Copper metabolism and cuproptosis in human malignancies: Unraveling the complex interplay for therapeutic insights DOI Creative Commons

K.M. Abdullah,

Jyoti Kaushal,

Simran Takkar

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e27496 - e27496

Published: March 1, 2024

Copper, a vital trace element, orchestrates diverse cellular processes ranging from energy production to antioxidant defense and angiogenesis. Copper metabolism cuproptosis are closely linked in the context of human diseases, with particular focus on cancer. Cuproptosis refers specific type copper-mediated cell death or copper toxicity triggered by disruptions within cells. This phenomenon encompasses spectrum mechanisms, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum perturbations metal ion equilibrium. Mechanistically, is driven binding lipoylated enzymes tricarboxylic acid (TCA) cycle. interaction participates protein aggregation proteotoxic ultimately culminating death. Targeting its associated pathways cancer cells holds therapeutic potential selectively targeting eliminating cancerous Strategies modulate levels, enhance excretion, interfere cuproptotic being explored identify novel targets for therapy improve patient outcomes. Understanding relationship between malignancies remains an active area research. review provides comprehensive overview association metabolism, homeostasis, cancers, explicitly emphasizing mechanism implications pathogenesis. Additionally, we emphasize aspects treatment.

Language: Английский

Citations

16
Metal ions and nanometallic materials in antitumor immunity: Function, application, and perspective DOI Creative Commons
Feiyang Shen, Yan Fang, Yijia Wu

et al.

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Jan. 19, 2023

The slightest change in the extra/intracellular concentration of metal ions results amplified effects by signaling cascades that regulate both cell fate within tumor microenvironment and immune status, which influences network antitumor immunity through various pathways. Based on fact influence cancer cells participate innate adaptive immunity, they are widely applied therapy as modulators. Moreover, nanomedicine possesses advantage precise delivery responsive release, can perfectly remedy drawbacks ions, such low target selectivity systematic toxicity, thus providing an ideal platform for ion application treatment. Emerging evidence has shown immunotherapy with nanometallic materials may significantly enhance therapeutic efficacy. Here, we focus physiopathology tumorigenesis discuss several breakthroughs regarding use immunotherapeutics. These findings demonstrate prominence ion-based prophylaxis, many new ideas basic research clinical application. Consequently, provide innovative insights into comprehensive understanding combined past few years.

Language: Английский

Citations

39
The expression of cuproptosis-related genes in hepatocellular carcinoma and their relationships with prognosis DOI Creative Commons
Xueying Zhao, Jin Chen,

Shangqi Yin

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 14, 2022

The mechanism of cuproptosis has recently been reported in lipoylated proteins the tricarboxylic acid (TCA) cycle. Besides, role copper was previously recognized cancer progression. We evaluated prognostic value cuproptosis-related gene expression hepatocellular carcinoma (HCC). Remarkable genes were selected both differential analysis and Kaplan-Meier survival from ninety-six using Cancer Genome Atlas (TCGA) database. relationships between clinical characteristics performed with Wilcoxon signed-rank test, Kruskal-Wallis logistic regression. Clinicopathologic factors correlated overall HCCs conducting univariate multivariate Cox regression analysis. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) Human Protein (HPA) databases utilized to verify results. Furthermore, Set Enrichment (GSEA) identified potential key pathways that dominate HCC. Elevated ATP7A, SLC25A3, SCO2, COA6, TMEM199, ATP6AP1, LIPT1, DLAT, PDHA1, MTF1, ACP1, FDX2, NUBP2, CIAPIN1, ISCA2 NDOR1 expression, as well declined AOC1, FDX1, MT-CO1, ACO1 significantly emerged HCC tumor tissues associated poor survival. expressions screened prominently related features. GSEA many signaling (such natural killer cell mediated cytotoxicity, TCA cycle, glutathione metabolism, ATP-binding cassette (ABC) transporters, Notch pathway, ErbB metabolism xenobiotics by cytochrome p450) differentially enriched varying degrees expression. twenty might be new candidate biomarkers for

Language: Английский

Citations

38
Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma DOI Creative Commons

Yu‐Ting Xue,

Xuejiao Jiang,

Junrong Wang

et al.

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Jan. 5, 2023

Abstract Head and neck cancer is a malignant tumour with high mortality rate characterized by late diagnosis, recurrence metastasis rates, poor prognosis. squamous cell carcinoma (HNSCC) the most common type of head cancer. Various factors are involved in occurrence development HNSCC, including external inflammatory stimuli oncogenic viral infections. In recent years, studies on regulation death have provided new insights into biology therapeutic response such as apoptosis, necroptosis, pyroptosis, autophagy, ferroptosis, recently newly discovered cuproptosis. We explored how various deaths act unique defence mechanism against emergence they can be exploited to inhibit tumorigenesis progression, thus introducing regulatory (RCD) novel strategy for therapy. contrast accidental death, RCD controlled specific signal transduction pathways, TP53 signalling, KRAS NOTCH hypoxia metabolic reprogramming. this review, we describe molecular mechanisms nonapoptotic its relationship HNSCC discuss crosstalk between relevant signalling pathways cells. also highlight approaches elimination through RCD.

Language: Английский

Citations

28
Construction and validation of a cuproptosis-related prognostic model for glioblastoma DOI Creative Commons
Bohong Zhang, Lin Xie, Jiahao Liu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 6, 2023

Cuproptosis, a newly reported type of programmed cell death, takes part in the regulation tumor progression, treatment response, and prognosis. But specific effect cuproptosis-related genes (CRGs) on glioblastoma (GBM) is still unclear.The transcriptome data corresponding clinical GBM samples were downloaded from TCGA GEO databases. R software packages used to perform statistical analysis, consensus cluster survival Cox regression Lasso microenvironment analysis. The mRNA protein expression levels model-related detected by RT-qPCR Western blot assays, respectively.The profile CRGs 209 two separate datasets was obtained. Two cuproptosis subtypes, CRGcluster A B, identified There apparent differences prognosis, microenvironment, immune checkpoint between there 79 prognostic differentially expressed (DEGs). According DEGs, gene geneCluster identified, risk score model constructed validated. This consists five including PDIA4, DUSP6, PTPRN, PILRB, CBLN1. Ultimately, improve applicability model, nomogram established. Patients with low-risk have higher mutation burden predict longer OS than high-risk group. Moreover, related drug sensitivity negatively correlated CSC index.We successfully which can independently prognosis patients. These results further complement understanding provide new theoretical support for developing more effective strategy.

Language: Английский

Citations

27
Role of cuproptosis in understanding diseases DOI Open Access

Shihan Cao,

Qian Wang,

Zhenzhen Sun

et al.

Human Cell, Journal Year: 2023, Volume and Issue: 36(4), P. 1244 - 1252

Published: May 8, 2023

Language: Английский

Citations

26
Mechanisms of cuproptosis and its relevance to distinct diseases DOI

Qiao-mei Lou,

Feifan Lai,

Jingwei Li

et al.

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(7-8), P. 981 - 1006

Published: June 2, 2024

Language: Английский

Citations

11