EBF1, MYO6 and CALR expression levels predict therapeutic response in diffuse large B-cell lymphomas

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a hematological malignancy representing one-third of non-Hodgkin’s lymphoma cases. Notwithstanding immunotherapy in combination with chemotherapy (R-CHOP) is an effective therapeutic approach for DLBCL, a subset of patients encounters treatment resi...

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Main Authors: Alice Turdo, Miriam Gaggianesi, Caterina D’Accardo, Gaetana Porcelli, Sebastiano Di Bella, Dario Cricchio, Irene Pillitteri, Rossana Porcasi, Melania Lo Iacono, Francesco Verona, Chiara Modica, Narges Roozafzay, Ada Maria Florena, Giorgio Stassi, Salvatrice Mancuso, Matilde Todaro
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-11-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1266265/full
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author Alice Turdo
Miriam Gaggianesi
Caterina D’Accardo
Gaetana Porcelli
Sebastiano Di Bella
Dario Cricchio
Irene Pillitteri
Rossana Porcasi
Melania Lo Iacono
Francesco Verona
Chiara Modica
Narges Roozafzay
Ada Maria Florena
Giorgio Stassi
Salvatrice Mancuso
Matilde Todaro
Matilde Todaro
author_facet Alice Turdo
Miriam Gaggianesi
Caterina D’Accardo
Gaetana Porcelli
Sebastiano Di Bella
Dario Cricchio
Irene Pillitteri
Rossana Porcasi
Melania Lo Iacono
Francesco Verona
Chiara Modica
Narges Roozafzay
Ada Maria Florena
Giorgio Stassi
Salvatrice Mancuso
Matilde Todaro
Matilde Todaro
author_sort Alice Turdo
collection DOAJ
description BackgroundDiffuse large B-cell lymphoma (DLBCL) is a hematological malignancy representing one-third of non-Hodgkin’s lymphoma cases. Notwithstanding immunotherapy in combination with chemotherapy (R-CHOP) is an effective therapeutic approach for DLBCL, a subset of patients encounters treatment resistance, leading to low survival rates. Thus, there is an urgent need to identify predictive biomarkers for DLBCL including the elderly population, which represents the fastest-growing segment of the population in Western countries.MethodsGene expression profiles of n=414 DLBCL biopsies were retrieved from the public dataset GSE10846. Differentially expressed genes (DEGs) (fold change >1.4, p-value <0.05, n=387) have been clustered in responder and non-responder patient cohorts. An enrichment analysis has been performed on the top 30 up-regulated genes of responder and non-responder patients to identify the signatures involved in gene ontology (MSigDB). The more significantly up-regulated DEGs have been validated in our independent collection of formalin-fixed paraffin-embedded (FFPE) biopsy samples of elderly DLBCL patients, treated with R-CHOP as first-line therapy.ResultsFrom the analysis of two independent cohorts of DLBCL patients emerged a gene signature able to predict the response to R-CHOP therapy. In detail, expression levels of EBF1, MYO6, CALR are associated with a significant worse overall survival.ConclusionsThese results pave the way for a novel characterization of DLBCL biomarkers, aiding the stratification of responder versus non-responder patients.
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spelling doaj.art-b198c3f32aad41e698a82358a2a2963c2023-11-14T09:43:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12662651266265EBF1, MYO6 and CALR expression levels predict therapeutic response in diffuse large B-cell lymphomasAlice Turdo0Miriam Gaggianesi1Caterina D’Accardo2Gaetana Porcelli3Sebastiano Di Bella4Dario Cricchio5Irene Pillitteri6Rossana Porcasi7Melania Lo Iacono8Francesco Verona9Chiara Modica10Narges Roozafzay11Ada Maria Florena12Giorgio Stassi13Salvatrice Mancuso14Matilde Todaro15Matilde Todaro16Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, ItalyDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, ItalyDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, Palermo, ItalyDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, ItalyDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, ItalyDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, ItalyA.O.U.P. “Paolo Giaccone”, University of Palermo, Palermo, ItalyBackgroundDiffuse large B-cell lymphoma (DLBCL) is a hematological malignancy representing one-third of non-Hodgkin’s lymphoma cases. Notwithstanding immunotherapy in combination with chemotherapy (R-CHOP) is an effective therapeutic approach for DLBCL, a subset of patients encounters treatment resistance, leading to low survival rates. Thus, there is an urgent need to identify predictive biomarkers for DLBCL including the elderly population, which represents the fastest-growing segment of the population in Western countries.MethodsGene expression profiles of n=414 DLBCL biopsies were retrieved from the public dataset GSE10846. Differentially expressed genes (DEGs) (fold change >1.4, p-value <0.05, n=387) have been clustered in responder and non-responder patient cohorts. An enrichment analysis has been performed on the top 30 up-regulated genes of responder and non-responder patients to identify the signatures involved in gene ontology (MSigDB). The more significantly up-regulated DEGs have been validated in our independent collection of formalin-fixed paraffin-embedded (FFPE) biopsy samples of elderly DLBCL patients, treated with R-CHOP as first-line therapy.ResultsFrom the analysis of two independent cohorts of DLBCL patients emerged a gene signature able to predict the response to R-CHOP therapy. In detail, expression levels of EBF1, MYO6, CALR are associated with a significant worse overall survival.ConclusionsThese results pave the way for a novel characterization of DLBCL biomarkers, aiding the stratification of responder versus non-responder patients.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1266265/fulldiffuse large B-cell lymphomaR-CHOPtherapy resistanceelderly patientsgene expression signaturebiomarkers of response
spellingShingle Alice Turdo
Miriam Gaggianesi
Caterina D’Accardo
Gaetana Porcelli
Sebastiano Di Bella
Dario Cricchio
Irene Pillitteri
Rossana Porcasi
Melania Lo Iacono
Francesco Verona
Chiara Modica
Narges Roozafzay
Ada Maria Florena
Giorgio Stassi
Salvatrice Mancuso
Matilde Todaro
Matilde Todaro
EBF1, MYO6 and CALR expression levels predict therapeutic response in diffuse large B-cell lymphomas
Frontiers in Immunology
diffuse large B-cell lymphoma
R-CHOP
therapy resistance
elderly patients
gene expression signature
biomarkers of response
title EBF1, MYO6 and CALR expression levels predict therapeutic response in diffuse large B-cell lymphomas
title_full EBF1, MYO6 and CALR expression levels predict therapeutic response in diffuse large B-cell lymphomas
title_fullStr EBF1, MYO6 and CALR expression levels predict therapeutic response in diffuse large B-cell lymphomas
title_full_unstemmed EBF1, MYO6 and CALR expression levels predict therapeutic response in diffuse large B-cell lymphomas
title_short EBF1, MYO6 and CALR expression levels predict therapeutic response in diffuse large B-cell lymphomas
title_sort ebf1 myo6 and calr expression levels predict therapeutic response in diffuse large b cell lymphomas
topic diffuse large B-cell lymphoma
R-CHOP
therapy resistance
elderly patients
gene expression signature
biomarkers of response
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1266265/full
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