A glycolysis-related gene signatures in diffuse large B-Cell lymphoma predicts prognosis and tumor immune microenvironment

Cui, Yingying; Leng, Cathryn

doi:10.3389/fcell.2023.1070777

Cited by 8 publications

(7 citation statements)

References 55 publications

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“…B cells as immunomodulatory cells, positive mediators, and antigen-presenting cells play a role in modulating the immune response to cancer ( 83 ). We found that DLBCL with high CISD2Risk value exhibited increased B cell infiltrations in accord with several studies ( 47 , 77 , 84 , 85 ). B cells are part of the adaptive immune system and can produce antibodies against cancer cells.…”

Section: Discussionsupporting

confidence: 92%

“…We introduced the ESTIMATE algorithm to infer the fraction of stromal and immune cells in tumour samples based on single sample gene set enrichment analysis (ssGSEA). A higher stromal ( P < 0.05, Figures 6A, D ) or immune scores ( P < 0.05, Figures 6B, E ) suggested greater density of stromal or immune cells in the tumour immune microenvironment of DLBCL patients with low CISD2Risk value the ESTIMATE scores that represent the sum of the stromal or immune scores, which can infer tumour purity associated with poor prognosis ( 29 , 45 ), were negatively correlated with CISD2Risk value ( 46 , 47 ) ( P < 0.05, Figures 6C, F ). The CIBERSORT algorithm ( 30 ) was used to estimate the distribution and proportion of 22 immune cell types in DLBCL.…”

Section: Resultsmentioning

confidence: 96%

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

Zhang,

Lin,

et al. 2023

Front. Immunol.

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 96%

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

Zhang,

Lin,

et al. 2023

Front. Immunol.

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“…In addition, the metabolic status, such as glycolysis, of exhausted CD8 + TILs is reported to be abnormally active and is related to the resistance to ICB therapy [ 45 ]. A recent study has shown that the abnormal expression of glycolysis-related signature genes in DLBCL is related to the infiltration of CD8 + TILs and TIM3 expression [ 46 ], suggesting the possible role of glycolysis in TIM3/Galectin-9 pathway mediated CD8 + TILs exhaustion in DLBCL.…”

Section: Discussionmentioning

confidence: 99%

Diffuse large B-cell lymphoma: the significance of CD8+ tumor-infiltrating lymphocytes exhaustion mediated by TIM3/Galectin-9 pathway

Zhu,

Yang,

Chen

et al. 2024

J Transl Med

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Background Overexpression of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is related to the exhaustion of CD8+ tumor-infiltrating lymphocytes (TILs) in diffuse large B-cell lymphoma (DLBCL). However, the mechanism of TIM3-mediated CD8+TILs exhaustion in DLBCL remains poorly understood. Therefore, we aimed to clarify the potential pathway involved in TIM3-mediated CD8+TILs exhaustion and its significance in DLBCL. Methods The expression of TIM3 and its correlation with CD8+TILs exhaustion, the key ligand of TIM3, and the potential pathway of TIM3-mediated CD8+TILs exhaustion in DLBCL were analyzed using single-cell RNA sequencing and validated by RNA sequencing. The biological significance of TIM3-related pathway in DLBCL was investigated based on RNA sequencing, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction data. Finally, the possible regulatory mechanism of TIM3-related pathway in DLBCL was explored using single-cell RNA sequencing and RNA sequencing. Results Our results demonstrated that CD8+TILs, especially the terminally exhausted state, were the major clusters that expressed TIM3 in DLBCL. Galectin-9, mainly expressed in M2 macrophages, is the key ligand of TIM3 and can induce the exhaustion of CD8+TILs through TIM3/Galectin-9 pathway. Meanwhile, high TIM3/Galectin-9 enrichment is related to immunosuppressive tumor microenvironment, severe clinical manifestations, inferior prognosis, and poor response to CHOP-based chemotherapy, and can predict the clinical efficacy of immune checkpoint blockade therapy in DLBCL. Furthermore, the TIM3/Galectin-9 enrichment in DLBCL may be regulated by the IFN-γ signaling pathway. Conclusions Our study highlights that TIM3/Galectin-9 pathway plays a crucial role in CD8+TILs exhaustion and the immune escape of DLBCL, which facilitates further functional studies and could provide a theoretical basis for the development of novel immunotherapy in DLBCL.

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“…A workable strategy for risk classi cation and focused gene identi cation is bioinformatics analysis based on sequenced RNA data. Although risk analyzed rely on immune cell in ltration and energy metabolism have been developed by researchers [23,33,34] , our work has particular advantages over earlier research. First, by consensus clustering, two molecular clusters with noticeably contrasting outlooks and immunological states were found in our studies on glycolysis in patients with DLBCL.…”

Section: Discussionmentioning

confidence: 99%

The Prediction of diffuse large B-cell lymphoma by a Novel Glycolysis-Related Gene Signature

Yang

et al. 2023

Preprint

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Objectives Globally, diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30–40% of all cases of non-Hodgkin's lymphoma. There is often rapid enlargement of a single or multiple external nodes or nodules in patients. glycolysis is the process by which glucose transporters on the cell membrane transport glucose into the cell to split into two molecules of pyruvate. The large amounts of lactic acid produced by glycolysis are secreted extracellular to create an acidic microenvironment. This change leads to the remodeling of the cell matrix, which is essential for tumor cell proliferation. To date, only a few studies have attempted to determine whether glycolysis plays a prognostic role in DLBCL. Methods On DLBCL patients, we gathered RNA-seq data and clinical details from the TCGA and GEO databases. Based on glycolysis genes, we divided them into two clusters by consensus clustering method. The two discovered clusters were compared for survival, function, and tumor microenvironments (TME) using the K-M survival analysis, ESTIMATE, TIMER, and ssGSEA analysis. A variety of methods were used to elucidate the mechanisms involved, including GO, KEGG, GSVA, and GSEA. Utilizing the LASSO tool and multivariate Cox regression analysis, a predictive risk model for genes associated to glycolysis was formed, and its value was verified by calibration and ROC curve. Results As shown by the K-M survival curve and Tumor microenvironment analysis both clusters had significantly difference. the survival rate, Immune Score, Stromal Score and ESTIMATE Score of the C1 cluster was substantially higher than the C2 cluster. GO and KEGG analysis indicated that DEGs between the two clusters tended to be enriched in extracellular matrix and immune pathways. It was suggested by GSVA and GSEA analyses that glycolysis-associated genes (GRGs) expression perhaps connected to immunosuppression and poor prognosis in DLBCL patients. With DLBCL, factors such as risk models and clinical features can be combined to accurately predict a patient's prognosis. Conclusion Patients with DLBCL exhibit glycolysis-related gene expression that predicts their prognosis, as well as the tumor microenvironment.

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A glycolysis-related gene signatures in diffuse large B-Cell lymphoma predicts prognosis and tumor immune microenvironment

Cited by 8 publications

References 55 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

Diffuse large B-cell lymphoma: the significance of CD8+ tumor-infiltrating lymphocytes exhaustion mediated by TIM3/Galectin-9 pathway

The Prediction of diffuse large B-cell lymphoma by a Novel Glycolysis-Related Gene Signature

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