Diagnostic and prognostic implications of tumor expression of the GATA-3 gene in nodal peripheral T-cell lymphoma (nPTCL): Retrospective data from a Latin American cohort

Lage, Luis Alberto de Padua Covas; Brito, Cláudio Vinícius; Levy, Débora; Culler, Hebert Fabrício; Couto, Samuel Campanelli Freitas; Oliveira, Lucas Bassolli Alves de; Zerbini, Maria Cláudia Nogueira; Rocha, Vanderson; Pereira, Juliana

doi:10.1016/j.leukres.2022.106794

Cited by 4 publications

(1 citation statement)

References 30 publications

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“…CD4 , which encodes the CD4 membrane glycoprotein, assists the germinal center reaction and contributes to the activation, functions, and longevity of CD8 + T-cells and B-cells ( 25 ). GATA3 , which encodes a protein of the GATA family of transcription factors, is an important regulator of T-cell development and may be a biomarker associated with poor prognosis in distinct subtypes of nodal peripheral T-cell lymphoma ( 26 ). We found that the hub genes were mainly enriched in the T-cell receptor signaling pathway, T-cell selection, the regulation of IL-2 production, the adaptive immune response, and cytokine production.…”

Section: Discussionmentioning

confidence: 99%

Identification of immune-related genes and development of a prognostic model in mantle cell lymphoma

Zhang¹,

Shi²,

Wang³

et al. 2022

Ann Transl Med

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Background: The immune landscape, prognostic model, and molecular variations of mantle cell lymphoma (MCL) remain unclear. Hence, an integrated bioinformatics analysis of MCL datasets is required for the development of immunotherapy and the optimization of targeted therapies.Methods: Data were obtained from the Gene Expression Omnibus (GEO) database (GSE32018, GSE45717 and GSE93291). The differentially expressed immune-related genes were selected, and the hub genes were screened by three machine learning algorithms, followed by enrichment and correlation analyses. Next, MCL molecular clusters based on the hub genes were identified by K-Means clustering, the probably approximately correct (PAC) algorithm, and principal component analysis (PCA). The landscape of immune cell infiltration and immune checkpoint molecules in distinct clusters was explored by single-sample gene-set enrichment analysis (ssGSEA) as well as the CIBERSORT and xCell algorithms. The prognostic genes and prognostic risk score model for MCL clusters were identified by least absolute shrinkage and selection operator (LASSO)-Cox analysis and cross-validation for lambda. Correlation analysis was performed to explore the correlation between the screened prognostic genes and immune cells or immune checkpoint molecules.Results: Four immune-related hub genes (CD247, CD3E, CD4, and GATA3) were screened in MCL, mainly enriched in the T-cell receptor signaling pathway. Based on the hub genes, two MCL molecular clusters were recognized. The cluster 2 group had a significantly worse overall survival (OS), with downregulated hub genes, and a variety of activated immune effector cells declined. The majority of immune checkpoint molecules had also decreased. An efficient prognostic model was established, including six prognostic genes (LGALS2, LAMP3, ICOS, FCAMR, IGFBP4, and C1QA) differentially expressed between two MCL clusters. Patients with a higher risk score in the prognostic model had a poor prognosis.Furthermore, most types of immune cells and a range of immune checkpoint molecules were positively correlated with the prognostic genes.Conclusions: Our study identified distinct molecular clusters based on the immune-related hub genes, and showed that the prognostic model affected the prognosis of MCL patients. These hub genes, modulated immune cells, and immune checkpoint molecules might be involved in oncogenesis and could be potential prognostic biomarkers in MCL.

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Section: Discussionmentioning

confidence: 99%

Identification of immune-related genes and development of a prognostic model in mantle cell lymphoma

Zhang¹,

Shi²,

Wang³

et al. 2022

Ann Transl Med

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Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen–Results of a Real-Life Study From a Middle-Income Country

Lage

Brito

Barreto

et al. 2022

Clinical Lymphoma Myeloma and Leukemia

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Tumor mutation burden involving epigenetic regulatory genes and the RhoA GTPase predicts overall survival in nodal mature T-cell lymphomas

et al. 2022

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Nodal mature T-cell lymphomas (nMTCL) comprises a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena, including mutations in genes that control DNA methylation and histone deacetylation, in addition to inactivating mutations in the RhoA GTPase, play a central role in its pathogenesis and constitute potential new targets for therapeutic intervention. Tumor mutational burden (TMB) reflects the process of clonal evolution, predicts response to anti-cancer therapies and has emerged as a prognostic biomarker in several solid neoplasms; however, its potential prognostic impact remains unknown in nMTCL. In this study, we conducted Sanger sequencing of formalin-fixed paraffin-embedded (FFPE) diagnostic tumor samples using a target-panel to search for recurrent mutations involving the IDH-1/IDH-2, TET-2, DNMT3A and RhoA genes in 59 cases of nMTCL. For the first time, we demonstrated that high-TMB, defined by the presence of ≥ two mutations involving the aforementioned genes, was associated with decreased overall survival in nMTCL patients treated with CHOP-like regimens. Additionally, high-TMB was correlated with bulky disease, lower overall response rate, and higher mortality. Future studies using larger cohorts may validate our preliminary results that indicate TMB as a potential molecular biomarker associated with adverse prognosis in nMTCL.

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Diagnostic and prognostic implications of tumor expression of the GATA-3 gene in nodal peripheral T-cell lymphoma (nPTCL): Retrospective data from a Latin American cohort

Cited by 4 publications

References 30 publications

Identification of immune-related genes and development of a prognostic model in mantle cell lymphoma

Identification of immune-related genes and development of a prognostic model in mantle cell lymphoma

Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen–Results of a Real-Life Study From a Middle-Income Country

Tumor mutation burden involving epigenetic regulatory genes and the RhoA GTPase predicts overall survival in nodal mature T-cell lymphomas

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