A Novel Cuproptosis-Related Prognostic Gene Signature and Validation of Differential Expression in Clear Cell Renal Cell Carcinoma

Genes, Journal Year: 2022, Volume and Issue: 13(5), P. 851 - 851

Published: May 10, 2022

Clear cell renal carcinoma (ccRCC) is the most prevalent subtype of carcinoma, which characterized by metabolic reprogramming. Cuproptosis, a novel form death, highly linked to mitochondrial metabolism and mediated protein lipoylation. However, clinical impacts cuproptosis-related genes (CRGs) in ccRCC largely remain unclear. In current study, we systematically evaluated genetic alterations ccRCC. Our results revealed that CDKN2A, DLAT, DLD, FDX1, GLS, PDHA1 PDHB exhibited differential expression between normal tissues (|log2(fold change)| > 2/3 p < 0.05). Utilizing an iterative sure independence screening (SIS) method, separately constructed prognostic signature CRGs for predicting overall survival (OS) progression-free (PFS) patients. The score yielded area under curve (AUC) 0.658 0.682 prediction 5-year OS PFS, respectively. Kaplan−Meier analysis OS, higher risk gene was significantly correlated with worse (HR = 2.72 (2.01−3.68), log-rank 1.76 × 10−7). Patients had shorter PFS 2.83 (2.08−3.85), 3.66 Two independent validation datasets (GSE40435 (N 101), GSE53757 72)) were collected meta-analysis, suggesting CDKN2A (log2(fold change) 1.46, 95%CI: 1.75−2.35) showed while DLAT −0.54, −0.93−−0.15) FDX1 −1.01, −1.61−−0.42) lowly expressed. also associated immune infiltration levels programmed death 1 (PD-1) (CDKN2A: r 0.24, 2.14 10−8; FDX1: −0.17, 1.37 10−4). conclusion, could serve as potential predictor patients may offer insights into cancer treatment.

Language: Английский

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Cuproptosis: Cellular and molecular mechanisms underlying copper-induced cell death

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(10), P. 1786 - 1787

Published: May 1, 2022

Language: Английский

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Cuproptosis Induced by ROS Responsive Nanoparticles with Elesclomol and Copper Combined with αPD‐L1 for Enhanced Cancer Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(22)

Published: March 14, 2023

Cuproptosis is a new cell death that depends on copper (Cu) ionophores to transport Cu into cancer cells, which induces death. However, existing are small molecules with short blood half-life making it hard enough cells. Herein, reactive oxygen species (ROS)-sensitive polymer (PHPM) designed, used co-encapsulate elesclomol (ES) and form nanoparticles (NP@ESCu). After entering ES Cu, triggered by excessive intracellular ROS, readily released. work in concerted way not only kill cells cuproptosis, but also induce immune responses. In vitro, the ability of NP@ESCu efficiently cuproptosis investigated. addition, change transcriptomes treated explored RNA-Seq. vivo, found mice model subcutaneous bladder cancer, reprograming tumor microenvironment. Additionally, further combined anti-programmed protein ligand-1 antibody (αPD-L1). This study provides first report combining nanomedicine can αPD-L1 for enhanced therapy, thereby providing novel strategy future therapy.

Language: Английский

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Cuproptosis: lipoylated TCA cycle proteins-mediated novel cell death pathway

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: May 13, 2022

Language: Английский

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Apoptotic cell death in disease—Current understanding of the NCCD 2023

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(5), P. 1097 - 1154

Published: April 26, 2023

Language: Английский

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Cuproptosis-Related Risk Score Predicts Prognosis and Characterizes the Tumor Microenvironment in Hepatocellular Carcinoma

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 11, 2022

Aims Cuproptosis is a recently identified form of programmed cell death; however, its role in hepatocellular carcinoma (HCC) remains unclear. Methods A set bioinformatic tools was integrated to analyze the expression and prognostic significance ferredoxin 1 ( FDX1 ), key regulator cuproptosis. cuproptosis-related risk score (CRRS) developed via correlation analyses, least absolute shrinkage selection operator (LASSO) Cox regression, multivariate regression. The metabolic features, mutation signatures, immune profile CRRS-classified HCC patients were investigated, CRRS therapy guidance analyzed. Results significantly downregulated HCC, high associated with longer survival time. high-CRRS group showed lower overall (OS) enriched cancer-related pathways. Mutation analyses revealed that had mutational frequency some tumor suppressors such as protein P53 TP53 ) Breast-cancer susceptibility gene (BRCA1)-associated BAP1 low catenin beta CTNNB1 ). Besides, an increase protumor infiltrates checkpoints. Moreover, area under curve (AUC) values predicting efficiency sorafenib non-responsiveness transcatheter arterial chemoembolization (TACE) reached 0.877 0.764, respectively. Significance signature helpful prediction guiding treatment for patients.

Language: Английский

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Comprehensive Analysis of Cuproptosis-Related Genes in Immune Infiltration and Prognosis in Melanoma

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: June 28, 2022

Skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) is the most lethal skin cancer with increasing incidence. Regulated cell death plays an important role in tumorigenesis and serves target for almost all treatment strategies. Cuproptosis recently identified copper-dependent regulated form that relies on mitochondria respiration. However, its remains unknown. The correlation of cuproptosis-related genes tumor prognosis far be understood, either. In present study, we explored between by accessing analyzing a public database found 11 out 12 were upregulated tissues three (LIPT1, PDHA1, SLC31A1) have predictive value prognosis. subgroup patients higher gene expression showed longer overall survival than those lower expression. We chose LIPT1 further exploration. was increased biopsies independent favorable prognostic indicator patients. Moreover, positively correlated PD-L1 negatively associated Treg infiltration. after receiving immunotherapy, indicating LIPT1. Finally, pan-cancer analysis indicated differentially expressed diverse cancers compared normal multiple immune checkpoints, especially PD-L1. It could serve some types. conclusion, our study demonstrated genes, LIPT1, melanoma, revealed infiltration thus providing new clues assessment immunotherapy melanoma.

Language: Английский

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Endoplasmic reticulum stress-mediated cell death in liver injury

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(12)

Published: Dec. 19, 2022

The endoplasmic reticulum is an important intracellular organelle that plays role in maintaining cellular homeostasis. Endoplasmic stress (ERS) and unfolded protein response (UPR) are induced when the body exposed to adverse external stimuli. It has been established ERS can induce different cell death modes, including autophagy, apoptosis, ferroptosis, pyroptosis, through three major transmembrane receptors on ER membrane, inositol requirement enzyme 1α, kinase-like kinase activating transcription factor 6. These modes of play occurrence development various diseases, such as neurodegenerative inflammation, metabolic liver injury. As largest organ, rich enzymes, carries out functions metabolism secretion, body's main site synthesis. Accordingly, a well-developed system present hepatocytes help perform its physiological functions. Current evidence suggests closely related stages injury, caused by may be key In addition, increasing modulating great potential for treating This article provided comprehensive overview relationship between four types death. Moreover, we discussed mechanism UPR injuries their therapeutic strategies.

Language: Английский

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Elesclomol: a copper ionophore targeting mitochondrial metabolism for cancer therapy

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Sept. 12, 2022

Abstract Elesclomol is an anticancer drug that targets mitochondrial metabolism. In the past, elesclomol was recognized as inducer of oxidative stress, but now it has also been found to suppress cancer by inducing cuproptosis. Elesclomol’s activity determined dependence on The metabolism stem cells, cells resistant platinum drugs, proteasome inhibitors, molecularly targeted and with inhibited glycolysis significantly enhanced. exhibited tremendous toxicity all three kinds cells. Elesclomol's highly dependent its transport extracellular copper ions, a process involved in discovery cuproptosis perfected specific suppressor mechanism elesclomol. For some time, failed yield favorable results oncology clinical trials, safety application confirmed. Research progress relationship between elesclomol, provides possibility explore reapplication clinic. New trials should selectively target types high attempt combine platinum, or inhibitors. Herein, particular will be presented, which may shed light better tumor treatment.

Language: Английский

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The therapeutic potential of targeting regulated non-apoptotic cell death

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(9), P. 723 - 742

Published: Aug. 7, 2023

Language: Английский

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