A prognostic immune risk score for diffuse large B‐cell lymphoma

Ma, Shu‐Yun; Tian, Xiao‐Peng; Cai, Jun; Su, Ning; Yu, Fang; Zhang, Yuchen; Wang, Jinni; Gale, Robert Peter; Cai, Qingqing

doi:10.1111/bjh.17478

Cited by 12 publications

(11 citation statements)

References 21 publications

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“…A high numbers M0, M1 macrophages correlated with better survival in DLBCL ( 75 , 77 ), and these data are consistent with our data. A lot of studies reported the lower amount of CD4 T cells and CD8 T cells in the lymphoma microenvironment correlated with poor survival ( 73 , 77 – 79 ). CD4 naïve T cell is considered essential to guarantee immune competence throughout life, can be activated after interaction with antigen Major Histocompatibility Complex (MHC) and differentiated into memory, effector, and suppressor cells ( 71 , 73 ).…”

Section: Discussionsupporting

confidence: 92%

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%

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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“…First, it only includes clinical indicators and ignores the important impact of molecular genetic heterogeneity on prognosis. Second, the use of Cox survival analysis alone to screen for independent prognostic factors is relatively outdated and cannot account for the non-linear associations between complex and diverse variables [ 45 , 46 ]. Relevant studies showed that even with the same IPI score, the prognoses of patients with DLBCL may differ significantly [ 5 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Artificial intelligence-based prognostic model accurately predicts the survival of patients with diffuse large B-cell lymphomas: analysis of a large cohort in China

Peng,

Su,

Guo

et al. 2024

BMC Cancer

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Background Diffuse large B-cell lymphomas (DLBCLs) display high molecular heterogeneity, but the International Prognostic Index (IPI) considers only clinical indicators and has not been updated to include molecular data. Therefore, we developed a widely applicable novel scoring system with molecular indicators screened by artificial intelligence (AI) that achieves accurate prognostic stratification and promotes individualized treatments. Methods We retrospectively enrolled a cohort of 401 patients with DLBCL from our hospital, covering the period from January 2015 to January 2019. We included 22 variables in our analysis and assigned them weights using the random survival forest method to establish a new predictive model combining bidirectional long-short term memory (Bi-LSTM) and logistic hazard techniques. We compared the predictive performance of our “molecular-contained prognostic model” (McPM) and the IPI. In addition, we developed a simplified version of the McPM (sMcPM) to enhance its practical applicability in clinical settings. We also demonstrated the improved risk stratification capabilities of the sMcPM. Results Our McPM showed superior predictive accuracy, as indicated by its high C-index and low integrated Brier score (IBS), for both overall survival (OS) and progression-free survival (PFS). The overall performance of the McPM was also better than that of the IPI based on receiver operating characteristic (ROC) curve fitting. We selected five key indicators, including extranodal involvement sites, lactate dehydrogenase (LDH), MYC gene status, absolute monocyte count (AMC), and platelet count (PLT) to establish the sMcPM, which is more suitable for clinical applications. The sMcPM showed similar OS results (P < 0.0001 for both) to the IPI and significantly better PFS stratification results (P < 0.0001 for sMcPM vs. P = 0.44 for IPI). Conclusions Our new McPM, including both clinical and molecular variables, showed superior overall stratification performance to the IPI, rendering it more suitable for the molecular era. Moreover, our sMcPM may become a widely used and effective stratification tool to guide individual precision treatments and drive new drug development.

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“…These findings suggest that the immune cells were associated with the NCCN-IPI/prognosis of DLBCL patients, and may act as potential markers to evaluate the prognosis of DLBCL patients. In fact, many researchers have built prognostic evaluation models for DLBCL based on immune cells ( 42 , 45 , 46 ). Our results may provide further supporting clues for future relevant researches.…”

Section: Discussionmentioning

confidence: 99%

Integration analysis of tumor metagenome and peripheral immunity data of diffuse large-B cell lymphoma

Zhang,

Han,

Xiao

et al. 2023

Front. Immunol.

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Background/purposeIt has been demonstrated that gut microbes are closely associated with the pathogenesis of lymphoma, but the gut microbe landscape and its association with immune cells in diffuse large B-cell lymphoma (DLBCL) remain largely unknown. In this study, we explored the associations between gut microbiota, clinical features and peripheral blood immune cell subtypes in DLBCL.MethodA total of 87 newly diagnosed DLBCL adults were enrolled in this study. The peripheral blood samples were collected from all patients and then submitted to immune cell subtyping using full-spectral flow cytometry. Metagenomic sequencing was applied to assess the microbiota landscape of 69 of 87 newly diagnosed DLBCL patients. The microbiotas and peripheral blood immune cell subsets with significant differences between different National Comprehensive Center Network-International Prognostic Indexes (NCCN-IPIs) (low-risk, low-intermediate-risk, intermediate-high-risk, high-risk) groups were screened.ResultsA total of 10 bacterial phyla, 31 orders and 455 bacteria species were identified in 69 patients with newly diagnosed DLBCL. The abundances of 6 bacteria, including Blautia sp.CAG 257, Actinomyces sp.S6 Spd3, Streptococcus parasanguinis, Bacteroides salyersiae, Enterococcus faecalls and Streptococcus salivarius were significantly different between the low-risk, low-intermediate-risk, intermediate-high-risk and high-risk groups, among which Streptococcus parasanguinis and Streptococcus salivarius were markedly accumulated in the high-risk group. The different bacteria species were mostly enriched in the Pyridoxal 5’-phosphate biosynthesis I pathway. In addition, we found that 2 of the 6 bacteria showed close associations with the different immune cell subtypes which were also identified from different NCCN-IPIs. In detail, the abundance of Bacteroides salyersiae was negatively correlated with Treg cells, CD38+ nonrescue exhausted T cells, nature killer 3 cells and CD38+CD8+ effector memory T cells, while the abundance of Streptococcus parasanguinis was negatively correlated with HLA-DR+ NK cells, CD4+ Treg cells, HLA-DR+ NKT cells and HLA-DR+CD94+CD159c+ NKT cells.ConclusionThis study first reveals the gut microbiota landscape of patients with newly diagnosed DLBCL and highlights the association between the gut microbiota and immunity, which may provide a new idea for the prognosis assessment and treatment of DLBCL.

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A prognostic immune risk score for diffuse large B‐cell lymphoma

Cited by 12 publications

References 21 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

Artificial intelligence-based prognostic model accurately predicts the survival of patients with diffuse large B-cell lymphomas: analysis of a large cohort in China

Integration analysis of tumor metagenome and peripheral immunity data of diffuse large-B cell lymphoma

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