Ferroptosis-Related Gene Signature: A New Method for Personalized Risk Assessment in Patients with Diffuse Large B-Cell Lymphoma

Chen, Huan; He, Yizi; Zeng, Ruolan; Li, Yajun; Chen, Siwei; Li, Yufeng; Xiao, Ling; Zhou, Hui

doi:10.2147/pgpm.s309846

Cited by 11 publications

(12 citation statements)

References 38 publications

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“…Few preceding studies implied that numerous genes might control provoked ferroptosis and their association with DLBCL patients' OS. 16 For instance, GPX4-positive and 8-hydroxydeoxyguanosine-negative patients had a significantly poor prognosis. And GPX4 overexpression inhibits ROS-induced cell death in DLBCL.…”

Section: Discussionmentioning

confidence: 99%

Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma

Zhang

et al. 2023

Technol Cancer Res Treat

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Background: Diffuse large B-cell lymphoma (DLBCL) is a well-differentiated disease, which makes the diagnosis and therapeutic strategy a difficult problem. While ferroptosis, as an iron-dependent form of regulated cell death, it plays an important role in causing several types of cancer. This study is aimed at exploring the prognostic value of ferroptosis-related genes in DLBCL. Methods: In our study, mRNA expression and matching clinical data of DLBCL patients were derived from Gene Expression Omnibus (GEO) database. First, multivariate cox regression model and nomogram which can predict the DLBCL patients’ prognosis were built and validated. The multigene signature was constructed and optimized by the least absolute shrinkage and selection operator (LASSO) cox regression model. Also, ferroptosis-related subtypes were developed by consistent cluster. Last but not least, we explored the association between categories of infiltrating immune cells and model genes’ expression. Results: Our results showed that 27 gene expressions were correlated with overall survival (OS) in the univariate cox regression analysis. A 4-gene signature was constructed through these genes to stratify patients into high-low risk groups using risk score derived from model (model 1:gene expression model). The OS of patients in the high-risk group was shorter than that of patients in the low-risk group in the TNM stage and clinically distinct subtypes (activated B cell [ABC], germinal center B cell [GCB]) ( P < .001). Furthermore, it was shown that the risk score was an independent factor in clinical cox regression model for OS (model 2:clinical model) (HR>1, P < .010). Besides, in consistent cluster analysis, ferroptosis prognosis status was different among 3 subtypes. Moreover, the correlation analysis between 4-gene with immune cells showed dendritic cells may be significantly associated with DLBCL. Conclusion: This research constructed an innovative ferroptosis-related gene signature for prognostic estimation of DLBCL patients. Solutions targeting ferroptosis could be an important therapeutic intervention for DLBCL.

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Section: Discussionmentioning

confidence: 99%

Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma

Zhang

et al. 2023

Technol Cancer Res Treat

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“…In addition, HIF1A was associated with increased tumor immunity and aggressive phenotypes in human cancers ( Chen et al, 2020 ). Ferroptosis-related genes associated with the overall survival in patients with diffuse large B-cell lymphoma have also been reported ( Chen H. et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Identifies Therapeutic Targets and the Mechanisms of Glutathione Action in Ferroptosis Occurring in Oral Cancer

Huang

Zhan

2022

Front. Pharmacol.

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Oral cancer (OC) is one of the most pernicious cancers with increasing incidence and mortality worldwide. Surgery is the primary approach for the treatment of early-stage OC, which reduces the quality of life of the patients. Therefore, there is an urgent need to discover novel treatments for OC. Targeting ferroptosis to induce cell death through the modulation of lipid oxidation has been used as a new approach to treat many cancers. Glutathione (GSH) is a coenzyme factor of GSH peroxidase 4, and it carries potential applicability in treating OC. By using network pharmacology and molecular docking followed by systematic bioinformatic analysis, we aimed to study GSH-targeting ferroptosis to treat OC. We identified 14 core molecular targets, namely, EGFR, PTGS2, HIF1A, VEGFA, TFRC, SLC2A1, CAV1, CDKN2A, SLC3A2, IFNG, NOX4, DDIT4, CA9, and DUSP1, involved in ferroptosis that were targeted by GSH for OC treatment. Functional characterization of these molecular targets showed their importance in the control of cell apoptosis, cell proliferation, and immune responses through various kinase activities such as the mitogen-activated protein kinase activity (e.g., ERK1 and ERK2 cascades) and modulation of TOR signaling (e.g., the HIF-1 signaling pathway). Molecular docking further revealed the direct binding of GSH with EGFR, PTGS2, and HIF1A proteins. These findings provide a novel insight into the targets of GSH in ferroptosis as well as possible molecular mechanisms involved, suggesting the possible use of GSH as a combined therapy for treating OC.

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“…The addition of CXCL2 enhances CLL cell survival. Chen reported that CXCL2 is a significant ferroptosis-related gene signature that can effectively classify DLBCL into different risk groups in terms of survival rate ( 14 ). Ferroptosis is a type of autophagy-dependent cell death.…”

Section: Discussionmentioning

confidence: 99%

“…The action of divalent iron and ester oxygenase catalyzes unsaturated fatty acids that are highly expressed on the cell membrane, leading to lipid peroxidation and inducing ferroptosis ( 10 ). Rapidly developing ferroptosis studies suggest the possibility of its prognostic significance in several cancers ( 11 – 14 ). Tumor cells are iron addicted, which means they are more dependent on iron than normal cells.…”

Section: Introductionmentioning

confidence: 99%

Identifying a novel ferroptosis-related prognostic score for predicting prognosis in chronic lymphocytic leukemia

Pan

Li²,

Xu³

et al. 2022

Front. Immunol.

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BackgroundChronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Although the treatment landscape for CLL is rapidly evolving, there are still some patients who develop drug resistance or disease refractory. Ferroptosis is a type of lipid peroxidation–induced cell death and has been suggested to have prognostic value in several cancers. Our research aims to build a prognostic model to improve risk stratification in CLL patients and facilitate more accurate assessment for clinical management.MethodsThe differentially expressed ferroptosis-related genes (FRGs) in CLL were filtered through univariate Cox regression analysis based on public databases. Least absolute shrinkage and selection operator (LASSO) Cox algorithms were performed to construct a prognostic risk model. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were performed to estimate the immune infiltration score and immune-related pathways. A total of 36 CLL patients in our center were enrolled in this study as a validation cohort. Moreover, a nomogram model was established to predict the prognosis.ResultsA total of 15 differentially expressed FRGs with prognostic significance were screened out. After minimizing the potential risk of overfitting, we constructed a novel ferroptosis-related prognostic score (FPS) model with nine FRGs (AKR1C3, BECN1, CAV1, CDKN2A, CXCL2, JDP2, SIRT1, SLC1A5, and SP1) and stratified patients into low- and high-risk groups. Kaplan–Meier analysis showed that patients with high FPS had worse overall survival (OS) (P<0.0001) and treatment-free survival (TFS) (P<0.0001). ROC curves evaluated the prognostic prediction ability of the FPS model. Additionally, the immune cell types and immune-related pathways were correlated with the risk scores in CLL patients. In the validation cohort, the results confirmed that the high-risk group was related to worse OS (P<0.0001), progress-free survival (PFS) (P=0.0140), and TFS (P=0.0072). In the multivariate analysis, only FPS (P=0.011) and CLL-IPI (P=0.010) were independent risk indicators for OS. Furthermore, we established a nomogram including FPS and CLL-IPI that could strongly and reliably predict individual prognosis.ConclusionA novel FPS model can be used in CLL for prognostic prediction. The model index may also facilitate the development of new clinical ferroptosis-targeted therapies in patients with CLL.

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Ferroptosis-Related Gene Signature: A New Method for Personalized Risk Assessment in Patients with Diffuse Large B-Cell Lymphoma

Cited by 11 publications

References 38 publications

Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma

Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma

Network Pharmacology Identifies Therapeutic Targets and the Mechanisms of Glutathione Action in Ferroptosis Occurring in Oral Cancer

Identifying a novel ferroptosis-related prognostic score for predicting prognosis in chronic lymphocytic leukemia

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