Gene set-based identification of two immune subtypes of diffuse large B cell lymphoma for guiding immune checkpoint blocking therapy

Li, Zhe; Duan, Ying; Ke, Qing; Wang, Mingyue; Cen, Hong; Zhu, Xiaodong

doi:10.3389/fgene.2022.1000460

Cited by 3 publications

(1 citation statement)

References 77 publications

(69 reference statements)

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“…Interestingly, previous studies conducted in 2015 also reported reduced expression of CD247 in NK/T-cell lymphoma [19]. The subsequent discovery made by scholars unveiled a signi cant association between the high expression of CD247 in DLBCL and enhanced overall survival [20]. Our studies consistently support the aforementioned perspective.…”

Section: Discussionsupporting

confidence: 88%

Revealing putative causal genes by establishing the causality between different lymphomas and immune cells

Lian,

Zhang,

Chen

et al. 2024

Preprint

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Background: The immune microenvironment not only plays a pivotal role in the pathogenesis of lymphoma but also serves as a critical determinant influencing disease progression and treatment resistance. However, there remains a dearth of comprehensive investigations exploring the causal relationship between various immune cell types and different lymphomas. Method: In this study, we employed common bidirectional two-sample mendelian randomization (MR) and linked disequilibrium score regression (LDSC) to investigate the causal relationship and genetic correlation between immune cells and various lymphomas. Additionally, we utilized the Mendelian randomization-based method of summary data-based MR (SMR), which incorporated genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) data from immune cells to identify genes associated with lymphoma. Furthermore, colocalization analysis and genetic correlation analysis were conducted for further validation of our findings. Results: The two-sample mendelian randomization approach was employed to identify the immune cell types that exhibit a causal relationship with different lymphomas. Additionally, the genetic correlation between these immune cells and malignant lymphomas was further analyzed using the linked disequilibrium score regression method, thereby enhancing the reliability of our findings. The SMR and colocalization analyses revealed several genes associated with these immune cells, thereby providing additional support for their putative role in the pathogenesis of lymphoma. Conclusions: Our study elucidates the intricate interplay between immune cells by employing genetic methodologies, thus offering insights for potential therapeutic targets and risk predictors in different subtypes of lymphoma treatments.

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Section: Discussionsupporting

confidence: 88%

Revealing putative causal genes by establishing the causality between different lymphomas and immune cells

Lian,

Zhang,

Chen

et al. 2024

Preprint

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Prognostic Significance of CDK1 Expression in Diffuse Large B-Cell Lymphoma

Chen,

Lu,

et al. 2024

Preprint

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Objective This study delves into the clinical implications and expression of CDK1 in diffuse large B-cell lymphoma (DLBCL). Methods Gene expression information from healthy subjects was sourced from the Genotype-Tissue Expression (GTEx) repository. Clinical details and survival statistics for DLBCL patients came from the Gene Expression Omnibus (GEO) archive (GSE10846). Patients were categorized based on CDK1 expression levels, and differences in clinical outcomes between the groups were examined. Univariate and multivariate Cox regression analyses were employed to ascertain whether CDK1 independently predicts DLBCL prognosis. The protein expression of CDK1 was gauged using immunohistochemistry. Additionally, we investigated the outcome of CDK1 inhibition on DLBCL cell growth and cell death using Cell Counting Kit-8 (CCK-8) and flow cytometry. Results In the control group, CDK1 was predominantly observed in the hematopoietic and reproductive systems. CDK1 levels in DLBCL patients were notably elevated compared to controls. Significant differences were noted in the LDH ratio and overall survival based on CDK1 expression. Statistical analyses confirmed CDK1 as an independent predictor of DLBCL outcomes. Elevated CDK1 protein was observed in a significant number of DLBCL samples, contrasting with normal lymph node samples from individuals without lymphoma. An inhibitor, Ro-3306, curtailed DLBCL cell growth and enhanced cell death in vitro. Conclusion Elevated CDK1 levels correlate with poor prognosis in DLBCL.

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Characterizing the Mutational Landscape of Diffuse Large B-Cell Lymphoma in a Prospective Cohort of Mexican Patients

Candelaria,

Cerrato-Izaguirre,

Gutierrez

et al. 2024

IJMS

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Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell malignancy worldwide. Molecular classifications have tried to improve cure rates. We prospectively examined and correlated the mutational landscape with the clinical features and outcomes of 185 Mexican patients (median age 59.3 years, 50% women) with newly diagnosed DLBCL. A customized panel of 79 genes was designed, based on previous international series. Most patients had ECOG performance status (PS) < 2 (69.2%), advanced-stage disease (72.4%), germinal-center phenotype (68.1%), and double-hit lymphomas (14.1%). One hundred and ten (59.5%) patients had at least one gene with driver mutations. The most common mutated genes were as follows: TP53, EZH2, CREBBP, NOTCH1, and KMT2D. The median follow-up was 42 months, and the 5-year relapse-free survival (RFS) and overall survival (OS) rates were 70% and 72%, respectively. In the multivariate analysis, both age > 50 years and ECOG PS > 2 were significantly associated with a worse OS. Our investigation did not reveal any discernible correlation between the presence of a specific mutation and survival. In conclusion, using a customized panel, we characterized the mutational landscape of a large cohort of Mexican DLBCL patients. These results need to be confirmed in further studies.

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Gene set-based identification of two immune subtypes of diffuse large B cell lymphoma for guiding immune checkpoint blocking therapy

Cited by 3 publications

References 77 publications

Revealing putative causal genes by establishing the causality between different lymphomas and immune cells

Revealing putative causal genes by establishing the causality between different lymphomas and immune cells

Prognostic Significance of CDK1 Expression in Diffuse Large B-Cell Lymphoma

Characterizing the Mutational Landscape of Diffuse Large B-Cell Lymphoma in a Prospective Cohort of Mexican Patients

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