Analysis of endoplasmic reticulum stress-related gene signature for the prognosis and pattern in diffuse large B cell lymphoma

Zhang, Chaofeng; Lin, Qi; Li, Chaoqi; Chen, Zhimin; Deng, Mengmeng; Weng, Huixin; Zhu, Xiongpeng

doi:10.1038/s41598-023-38568-x

Cited by 3 publications

(1 citation statement)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using public databases ( 17 – 22 ), we found upregulated CISD2 as an appropriate diagnostic factors and a unfavorable prognostic indicator in DLBCL. Recent studies demonstrated that a clinical risk model included multiple genes is helpful to better implement the eligible diagnostic and the favorably prognostic criteria in DLBCL patients ( 52 – 55 ). Here, we developed a CISD2-related risk model (CISD2Risk) based on CISD2 related genes using LASSO Cox regression analysis in the GSE117556 dataset, and performed external validation (GSE181063 dataset) for its performance.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma

Zhang,

Lin,

et al. 2023

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma in adults. CDGSH iron sulfur domain 2 (CISD2) is an iron–sulfur protein and plays a critical role of cell proliferation. The aberrant expression of CISD2 is associated with the progression of multiple cancers. However, its role in DLBCL remains unclear.MethodsThe differential expression of CISD2 was identified via public databases, and quantitative real-time PCR (qRT-PCR) and western blot were used to identifed the expression of CISD2. We estimated the impact of CISD2 on clinical prognosis using the Kaplan-Meier plotter. Meanwhile, the drug sensitivity of CISD2 was assessed using CellMiner database. The 100 CISD2-related genes from STRING obtained and analyzed using the LASSO Cox regression. A CISD2 related signature for risk model (CISD2Risk) was established. The PPI network of CISD2Risk was performed, and functional enrichment was conducted through the DAVID database. The impacts of CISD2Risk on clinical features were analyzed. ESTIMATE, CIBERSORT, and MCP-counter algorithm were used to identify CISD2Risk associated with immune infiltration. Subsequently, Univariate and multivariate Cox regression analysis were applied, and a prognostic nomogram, accompanied by a calibration curve, was constructed to predict 1-, 3-, and 5-years survival probabilities.ResultsCISD2 was upregulated in DLBCL patients comparing with normal controls via public datasets, similarly, CISD2 was highly expressed in DLBCL cell lines. Overexpression of CISD2 was associated with poor prognosis in DLBCL patients based on the GSE31312, the GSE32918, and GSE93984 datasets (P<0.05). Nine drugs was considered as a potential therapeutic agents for CISD2. By using the LASSO cox regression, twenty seven genes were identified to construct CISD2Risk, and biological functions of these genes might be involved in apoptosis and P53 signaling pathway. The high CISD2Risk value had a worse prognosis and therapeutic effect (P<0.05). The higher stromal score, immune score, and ESTIMATE score were associated with lowe CISD2Risk value, CISD2Risk was negatively correlated with several immune infiltrating cells (macrophages M0 and M1, CD8 T cells, CD4 naïve T cells, NK cell, etc) that might be correlated with better prognosis. Additionally, The high CISD2Risk was identified as an independent prognostic factor for DLBCL patients using both univariate and multivariate Cox regression. The nomogram produced accurate predictions and the calibration curves were in good agreement.ConclusionOur study demonstrates that high expression of CISD2 in DLBCL patients is associated with poor prognosis. We have successfully constructed and validated a good prognostic prediction and efficacy monitoring for CISD2Risk that included 27 genes. Meanwhile, CISD2Risk may be a promising evaluator for immune infiltration and serve as a reference for clinical decision-making in DLBCL patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma

Zhang,

Lin,

et al. 2023

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

Inhibition of CISD2 enhances sensitivity to doxorubicin in diffuse large B-cell lymphoma by regulating ferroptosis and ferritinophagy

Zhang,

Zhan,

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

BackgroundCDGSH iron-sulfur domain 2 (CISD2), an iron-sulfur protein with a [2Fe-2S] cluster, plays a pivotal role in the progression of various cancers, including Diffuse Large B-cell Lymphoma (DLBCL). However, the mechanisms by which CISD2 regulates the occurrence and development of DLBCL remain to be fully elucidated.MethodsThe potential role of CISD2 as a predictive marker in DLBCL patients treated with the R-CHOP regimen was investigated through bioinformatics analysis and clinical cohort studies. DLBCL cell lines (SUDHL-4 and HBL-1) were employed in this research. Adenoviral (AV) plasmids were used to either silence or overexpress CISD2 in these DLBCL cell lines. Additionally, the induction of ferroptosis in DLBCL cell lines was assessed. Various parameters, including cell proliferation, intracellular free iron levels, lipid peroxides, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP), were measured. Furthermore, the expression of proteins associated with ferroptosis and ferritinophagy was analyzed. Drug-resistant DLBCL cell lines were developed by gradually increasing doxorubicin (DOX) concentration over 6 months. The biological role of CISD2 in these drug-resistant DLBCL cell lines was subsequently assessed.ResultsElevated CISD2 levels were found to be associated with decreased sensitivity of DLBCL patients to the R-CHOP regimen, as indicated by bioinformatics and clinical cohort analysis. Silencing CISD2 significantly reduced cell proliferation, increased iron accumulation, depleted glutathione (GSH), and elevated malondialdehyde (MDA) levels, alongside the accumulation of ROS and increased MMP. Additionally, BECN1 and NCOA4 expressions were upregulated, while p62, FTH1, and GPX4 expressions were downregulated. Conversely, overexpression of CISD2 reversed these effects. Treatment of DLBCL cell lines with Erastin led to decreased CISD2 levels. Notably, in drug-resistant DLBCL cell lines, CISD2 knockdown promoted ferroptosis and ferritinophagy, restoring sensitivity to DOX and enhancing the efficacy of Erastin treatment.ConclusionOur findings suggest that CISD2 may play a role in the drug resistance observed in DLBCL patients. Inhibition of CISD2 could enhance ferroptosis and ferritinophagy, potentially improving the sensitivity of DLBCL cells to DOX treatment.

show abstract

Emerging Signatures of Hematological Malignancies from Gene Expression and Transcription Factor-Gene Regulations

Dall’Olio,

Magnani,

Casadei

et al. 2024

IJMS

View full text Add to dashboard Cite

Hematological malignancies are a diverse group of cancers developing in the peripheral blood, the bone marrow or the lymphatic system. Due to their heterogeneity, the identification of novel and advanced molecular signatures is essential for enhancing their characterization and facilitate its translation to new pharmaceutical solutions and eventually to clinical applications. In this study, we collected publicly available microarray data for more than five thousand subjects, across thirteen hematological malignancies. Using PANDA to estimate gene regulatory networks (GRNs), we performed hierarchical clustering and network analysis to explore transcription factor (TF) interactions and their implications on biological pathways. Our findings reveal distinct clustering patterns among leukemias and lymphomas, with notable differences in gene and TF expression profiles. Gene Set Enrichment Analysis (GSEA) identified 57 significantly enriched KEGG pathways, highlighting both common and unique biological processes across HMs. We also identified potential drug targets within these pathways, emphasizing the role of TFs such as CEBPB and NFE2L1 in disease pathophysiology. Our comprehensive analysis enhances the understanding of the molecular landscape of HMs and suggests new avenues for targeted therapeutic strategies. These findings also motivate the adoption of regulatory networks, combined with modern biotechnological possibilities, for insightful pan-cancer exploratory studies.

show abstract

Analysis of endoplasmic reticulum stress-related gene signature for the prognosis and pattern in diffuse large B cell lymphoma

Cited by 3 publications

References 72 publications

Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma

Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma

Inhibition of CISD2 enhances sensitivity to doxorubicin in diffuse large B-cell lymphoma by regulating ferroptosis and ferritinophagy

Emerging Signatures of Hematological Malignancies from Gene Expression and Transcription Factor-Gene Regulations

Contact Info

Product

Resources

About