Development and validation of a disulfidptosis-related genes signature for predicting outcomes and immunotherapy in acute myeloid leukemia DOI Creative Commons
Han Gong,

Ying Zhang,

Xusheng Wu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 4, 2025

Background Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes and high recurrence. Disulfidptosis, novel form of programmed cell death driven by aberrant disulfide bonds F-actin collapse, provides insights into cancer progression treatment. Methods We investigated the correlation network prognostic values disulfidptosis-related genes (DRGs) in AML. Unsupervised clustering was performed to reveal distinct AML subtypes. implemented differential analysis enrichment explore difference subtypes biological processes. Least absolute shrinkage selection operator (LASSO) Cox model used generate signature. employed ESTIMATE, CIBERSORT, scRNA analyses assess tumor microenvironment Moreover, experiments validated functions PTPN6 CSK OCI-AML2 cells. Results identified 10 DRGs revealed two disulfidptosis significantly affected immune processes like interferon-gamma response MHC class II antigen presentation. LASSO algorithm established 6-gene signature (HLA-DRB5, CCDC124, PTPN6, HLA-DMA, CSK, ISG15) that predicted prognosis validation cohorts more robustly than other signatures. Disulfidptosis correlated cells, especially monocytes. The risk subgroups differed susceptibilities multiple chemotherapy drugs, indicating as potential therapeutic target. Knockdown inhibited proliferation cells increased apoptosis. Conclusions Our study DRG prognoses immunomodulation, establishing robust for predicting may enhance precision medicine treatment strategies.

Language: Английский

Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF‐1α/SLC7A11 pathway DOI

Siyu Yuan,

Can Wei,

Guofang Liu

et al.

Cell Proliferation, Journal Year: 2021, Volume and Issue: 55(1)

Published: Nov. 22, 2021

Evidences demonstrate that sorafenib alleviates liver fibrosis via inhibiting HSC activation and ECM accumulation. The underlying mechanism remains unclear. Ferroptosis, a novel programmed cell death, regulates diverse physiological/pathological processes. In this study, we aim to investigate the functional role of ferroptosis in anti-fibrotic effect sorafenib.

Language: Английский

Citations

269
Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity DOI Creative Commons
Bartosz Wiernicki,

Sophia Maschalidi,

Jonathan J. Pinney

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 27, 2022

Abstract Immunogenic cell death significantly contributes to the success of anti-cancer therapies, but immunogenicity different modalities widely varies. Ferroptosis, a form that is characterized by iron accumulation and lipid peroxidation, has not yet been fully evaluated from this perspective. Here we present an inducible model ferroptosis, distinguishing three phases in process—‘initial’ associated with ‘intermediate’ correlated ATP release ‘terminal’ recognized HMGB1 loss plasma membrane integrity—that serves as tool study immune responses ferroptotic cancer cells. Co-culturing cells dendritic (DC), reveals ‘initial’ decrease maturation DC, are poorly engulfed, dampen antigen cross-presentation. DC loaded ferroptotic, contrast necroptotic, fail protect against tumor growth. Adding immunogenic apoptotic dramatically reduces their prophylactic vaccination potential. Our thus shows ferroptosis negatively impacts presenting hence adaptive response, which might hinder therapeutic applications induction.

Language: Английский

Citations

219
Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis DOI

Yaqing Zhou,

Hanxiao Zhou, Lei Hua

et al.

Free Radical Biology and Medicine, Journal Year: 2021, Volume and Issue: 171, P. 55 - 68

Published: May 8, 2021

Language: Английский

Citations

179
The crosstalk of CD8+ T cells and ferroptosis in cancer DOI Creative Commons
Zhengjun Lin,

Songzhu Zou,

Kunming Wen

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 15, 2024

Ferroptosis is an iron-dependent, novel form of programmed cell death characterized by lipid peroxidation and glutathione depletion widespread in a variety diseases. CD8+ T cells are the most important effector cytotoxic cells, capable specifically recognizing killing cancer cells. Traditionally, thought to induce mainly through perforin granzyme, Fas-L/Fas binding. In recent years, cell-derived IFN-γ was found promote ferroptosis multiple mechanisms, including upregulation IRF1 IRF8, downregulation system XC-, while shown enhance anti-tumor effects heating tumor immune microenvironment exposure release tumor-associated specific antigens, which results positive feedback pathway. Unfortunately, intra-tumoral more sensitive than limits application inducers cancer. addition, susceptible being regulated other TME, such as macrophages, dendritic Treg, bone marrow-derived immunosuppressive Together, these factors build complex network Therefore, we aim integrate relevant studies reveal potential mechanisms crosstalk between ferroptosis, summarize preclinical models therapy find new therapeutic strategies this review.

Language: Английский

Citations

25
Ferroptosis‐related gene signature associates with immunity and predicts prognosis accurately in patients with osteosarcoma DOI Creative Commons
Ting Lei, Hu Qian, Pengfei Lei

et al.

Cancer Science, Journal Year: 2021, Volume and Issue: 112(11), P. 4785 - 4798

Published: Sept. 10, 2021

Abstract Osteosarcoma has been the most common malignant bone tumor in children and adolescents, while 5‐y survival of osteosarcoma patients gained no significant improvement over past decades. This study aimed to explore role ferroptosis‐related genes (FRGs) development prognosis osteosarcoma. The datasets including RNA sequencing data clinical information were acquired from TRGET Gene Expression Omnibus (GEO) databases. identification molecular subgroups with different FRG expression patterns was achieved through nonnegative matrix factorization (NMF) clustering. prognostic model constructed using least absolute shrinkage selection operator (LASSO) algorithm multivariate Cox regression analysis. ESTIMATE applied for determining stromal score, immune ESTIMA purity patients. Functional analyses Ontology (GO), Kyoto Encyclopedia Genes Genomes (KEGG) analyses, Set Enrichment Analysis (GSEA), Variation (GSVA) conducted underlying mechanisms Two FRGs identified. higher score more active status showed better survival. On basis FRGs, a nomogram integrating characteristics their prediction efficiency well validated. functional enrichment analysis that these differentially expressed mainly enriched immunity‐related signaling pathways, indicating may affect by regulating microenvironment. profiles closely related immunity interaction between ferroptosis could provide new insight into exploration targeted therapies

Language: Английский

Citations

88
Identification of a Ferroptosis-Related Signature Model Including mRNAs and lncRNAs for Predicting Prognosis and Immune Activity in Hepatocellular Carcinoma DOI Creative Commons
Zi-An Chen, Hui Tian, Dongmei Yao

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Sept. 9, 2021

Background Ferroptosis is a novel form of regulated cell death involved in tumor progression. The role ferroptosis-related lncRNAs hepatocellular carcinoma (HCC) remains unclear. Methods RNA-seq and clinical data for HCC patients were downloaded from Cancer Genome Atlas (TCGA) Genomic Data Commons (GDC) portal. Bioinformatics methods, including weighted gene coexpression network analysis (WGCNA), Cox regression, least absolute shrinkage selection operator (LASSO) analysis, used to identify signature markers diagnosis/prognosis. microenvironment, immune infiltration functional enrichment compared between the low-risk high-risk groups. Subsequently, small molecule drugs targeting components predicted via L1000FWD PubChem databases. Results prognostic model consisted 2 mRNAs (SLC1A5 SLC7A11) 8 (AC245297.3, MYLK-AS1, NRAV, SREBF2-AS1, AL031985.3, ZFPM2-AS1, AC015908.3, MSC-AS1). areas under curves (AUCs) 0.830 0.806 training test groups, respectively. Decision curve (DCA) revealed that performed better than all pathological characteristics. Multivariate regression showed risk score was an independent factor. survival probability low- could be clearly distinguished by principal component (PCA) plot. divided into two distinct groups terms status, especially checkpoint expression, which further supported Gene Ontology (GO) biological process, Kyoto Encyclopedia Genes Genomes (KEGG) analysis. Finally, several (SIB-1893, geldanamycin PD-184352, etc) identified future reference. Conclusion We constructed new mRNA/lncRNA patients. can prediction evaluation, providing reference immunotherapies targeted therapies.

Language: Английский

Citations

59
Quercetin Alleviates Deoxynivalenol-Induced Intestinal Damage by Suppressing Inflammation and Ferroptosis in Mice DOI

Yingrong Ye,

Mingzhen Jiang,

Xinyao Hong

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(28), P. 10761 - 10772

Published: July 1, 2023

Deoxynivalenol (DON), one of the most prevalent mycotoxins found in food and feed, can cause gastrointestinal inflammation systemic immunosuppression, presenting a serious hazard to human animal health. Quercetin (QUE) is plant polyphenol with anti-inflammatory antioxidant properties. In this research, we investigated potential function QUE as treatment for DON-induced intestinal damage. Thirty male specific-pathogen-free BALB/c mice were randomly allocated (50 mg/kg) and/or DON (0, 0.5, 1, 2 mg/kg). We that attenuated damage by improving jejunal structural injury changing tight junction proteins (claudin-1, claudin-3, ZO-1, occludin) levels. also suppressed DON-triggered inhibiting TLR4/NF-κB signaling pathway. Meanwhile, decreased oxidative stress caused enhancing concentrations SOD GSH, while diminishing contents MDA. particular, reduced ferroptosis. elevated TfR 4HNE levels, along transcription levels ferroptosis-related genes (PTGS2, ACSL4, HAMP1) mRNA FTH1, SLC7A11, GPX4, FPN1, FSP1, all which reversed treatment. Our findings imply alleviates pathway study, elucidate toxicological mechanism DON, provide basic foundation or theory future prevention treatment, explore strategies prevent alleviate DON's hazardous effects.

Language: Английский

Citations

34
SMURF2 predisposes cancer cell toward ferroptosis in GPX4-independent manners by promoting GSTP1 degradation DOI Creative Commons
Wenxin Zhang,

Junren Dai,

Guixue Hou

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(23), P. 4352 - 4369.e8

Published: Nov. 27, 2023

Language: Английский

Citations

32
Ferroptosis in gastrointestinal cancer: from mechanisms to implications DOI Creative Commons
Ruoxi Zhang, Rui Kang, Daolin Tang

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 561, P. 216147 - 216147

Published: March 24, 2023

Language: Английский

Citations

26
CAR memory–like NK cells targeting the membrane proximal domain of mesothelin demonstrate promising activity in ovarian cancer DOI Creative Commons
Mubin Tarannum, Khanhlinh Dinh,

Juliana Vergara

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(28)

Published: July 12, 2024

Epithelial ovarian cancer (EOC) remains one of the most lethal gynecological cancers. Cytokine-induced memory–like (CIML) natural killer (NK) cells have shown promising results in preclinical and early-phase clinical trials. In current study, CIML NK demonstrated superior antitumor responses against a panel EOC cell lines, increased expression activation receptors, up-regulation genes involved cycle/proliferation down-regulation inhibitory/suppressive genes. transduced with chimeric antigen receptor (CAR) targeting membrane-proximal domain mesothelin (MSLN) further improved MSLN-expressing patient-derived xenograft tumor cells. CAR arming subtanstially reduced their dysfunction ascites fluid transcriptomic changes related to altered metabolism tonic signaling as potential mechanisms. Lastly, adoptive transfer MSLN-CAR remarkable inhibition growth prevented metastatic spread mice, supporting an effective therapeutic strategy EOC.

Language: Английский

Citations

10