Overexpression of OCT-1 gene is a biomarker of adverse prognosis for diffuse large B-cell lymphoma (DLBCL): data from a retrospective cohort of 77 Brazilian patients

Abstract Background OCT-1 gene is a member of the POU-homeodomain family of transcriptional regulators of B-lymphocyte differentiation by controlling expression of B-cell specific genes. BCL-2 gene is a potent inhibitor of apoptosis and it is essential during B-cell differentiation into germinal cen...

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Main Authors: Gisele R. Gouveia, Suzete C. Ferreira, Sheila A. C. Siqueira, Luis Alberto de Pádua Covas Lage, Abrahão E. Hallack Neto, Renata de Oliveira Costa, Juliana Pereira
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Language:English
Published: BMC 2020-10-01
Series:BMC Cancer
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Online Access:http://link.springer.com/article/10.1186/s12885-020-07553-2
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author Gisele R. Gouveia
Suzete C. Ferreira
Sheila A. C. Siqueira
Luis Alberto de Pádua Covas Lage
Abrahão E. Hallack Neto
Renata de Oliveira Costa
Juliana Pereira
author_facet Gisele R. Gouveia
Suzete C. Ferreira
Sheila A. C. Siqueira
Luis Alberto de Pádua Covas Lage
Abrahão E. Hallack Neto
Renata de Oliveira Costa
Juliana Pereira
author_sort Gisele R. Gouveia
collection DOAJ
description Abstract Background OCT-1 gene is a member of the POU-homeodomain family of transcriptional regulators of B-lymphocyte differentiation by controlling expression of B-cell specific genes. BCL-2 gene is a potent inhibitor of apoptosis and it is essential during B-cell differentiation into germinal center. These genes may be expressed in diffuse large B-cell lymphoma (DLBCL), but the role of BCL-2 in its prognosis has been contradictory, and OCT-1 has yet to be tested. Methods In this study, we aimed to investigate the prognostic impact of OCT-1 and BCL-2 expression in DLBCL treated in the real world with immunochemotherapy in a single center. BCL-2 and OCT-1 genes were available in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR was isolated from formalin-fixed paraffin-embedded samples. The values obtained for gene expression were transformed in categorical variable according to their median. Results Cohort median age was 54.5 years (15–84), 49 (50%) were male, 38/77 (49.4%) and 40/77 (51.9%) presented OCT-1 and BCL-2 expression ≥ median, respectively. The overall response rate (ORR) in all patients was 68.4% (67/98), 65,3% (64/98) of patients acquired complete response, and 3.1% (3/98) partial response, while 6.1% (6/98) were primary refractory. The median follow-up was 3.77 years (95% CI: 3.2–4.1), with 5.43 (95% CI: 2.2-NR) of overall survival (OS) and 5.15 years (95% CI: 2.9-NA) of progression free survival (PFS). OCT-1 ≥ median was associated with shorter OS at univariate analysis (p = 0.013; [HR] 2.450, 95% CI: 1.21–4.96) and PFS (p = 0.019; [HR] 2.270, 95%CI: 1.14–4.51) and BCL-2 gene overexpression presented worse PFS (p = 0.043, [HR] 2.008, 95% CI: 1.02–3.95). At multivariate analysis, OCT-1 overexpression was associated with poor PFS (p = 0.035, [HR] 2.22, 95% CI: 1.06–4.67). Conclusion In this study, we showed that overexpression of OCT1 gene was an independent prognostic factor of adverse outcomes in DLBCL.
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spelling doaj.art-4df2e8579d1d425188c83eb3659ef18c2022-12-21T22:44:37ZengBMCBMC Cancer1471-24072020-10-012011910.1186/s12885-020-07553-2Overexpression of OCT-1 gene is a biomarker of adverse prognosis for diffuse large B-cell lymphoma (DLBCL): data from a retrospective cohort of 77 Brazilian patientsGisele R. Gouveia0Suzete C. Ferreira1Sheila A. C. Siqueira2Luis Alberto de Pádua Covas Lage3Abrahão E. Hallack Neto4Renata de Oliveira Costa5Juliana Pereira6Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Faculty of Medicine, University of Sao Paulo’s Medical School (FM-USP)Department of Molecular Biology, Pró-Sangue Foundation, Sao Paulo Blood BankDepartment of Pathology, Hospital das Clínicas – Faculty of Medicine, Sao Paulo University (HC-FM-USP)Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Faculty of Medicine, University of Sao Paulo’s Medical School (FM-USP)Department of Hematology and Hemotherapy, University of Juiz de Fora (UJF)Department of Hematology and Hemotherapy, Centro Universitário Lusíadas (FCMS/UNILUS)Department of Hematology, Hemotherapy and Cell Therapy, Faculty of Medicine, Sao Paulo University (FM-USP)Abstract Background OCT-1 gene is a member of the POU-homeodomain family of transcriptional regulators of B-lymphocyte differentiation by controlling expression of B-cell specific genes. BCL-2 gene is a potent inhibitor of apoptosis and it is essential during B-cell differentiation into germinal center. These genes may be expressed in diffuse large B-cell lymphoma (DLBCL), but the role of BCL-2 in its prognosis has been contradictory, and OCT-1 has yet to be tested. Methods In this study, we aimed to investigate the prognostic impact of OCT-1 and BCL-2 expression in DLBCL treated in the real world with immunochemotherapy in a single center. BCL-2 and OCT-1 genes were available in 78.5% (77/98) DLBCL patients, and the RNA for quantitative real-time PCR was isolated from formalin-fixed paraffin-embedded samples. The values obtained for gene expression were transformed in categorical variable according to their median. Results Cohort median age was 54.5 years (15–84), 49 (50%) were male, 38/77 (49.4%) and 40/77 (51.9%) presented OCT-1 and BCL-2 expression ≥ median, respectively. The overall response rate (ORR) in all patients was 68.4% (67/98), 65,3% (64/98) of patients acquired complete response, and 3.1% (3/98) partial response, while 6.1% (6/98) were primary refractory. The median follow-up was 3.77 years (95% CI: 3.2–4.1), with 5.43 (95% CI: 2.2-NR) of overall survival (OS) and 5.15 years (95% CI: 2.9-NA) of progression free survival (PFS). OCT-1 ≥ median was associated with shorter OS at univariate analysis (p = 0.013; [HR] 2.450, 95% CI: 1.21–4.96) and PFS (p = 0.019; [HR] 2.270, 95%CI: 1.14–4.51) and BCL-2 gene overexpression presented worse PFS (p = 0.043, [HR] 2.008, 95% CI: 1.02–3.95). At multivariate analysis, OCT-1 overexpression was associated with poor PFS (p = 0.035, [HR] 2.22, 95% CI: 1.06–4.67). Conclusion In this study, we showed that overexpression of OCT1 gene was an independent prognostic factor of adverse outcomes in DLBCL.http://link.springer.com/article/10.1186/s12885-020-07553-2Diffuse large B-cell lymphoma (DLBCL)OCT-1 geneBCL-2 genePrognosisImmunochemotherapy
spellingShingle Gisele R. Gouveia
Suzete C. Ferreira
Sheila A. C. Siqueira
Luis Alberto de Pádua Covas Lage
Abrahão E. Hallack Neto
Renata de Oliveira Costa
Juliana Pereira
Overexpression of OCT-1 gene is a biomarker of adverse prognosis for diffuse large B-cell lymphoma (DLBCL): data from a retrospective cohort of 77 Brazilian patients
BMC Cancer
Diffuse large B-cell lymphoma (DLBCL)
OCT-1 gene
BCL-2 gene
Prognosis
Immunochemotherapy
title Overexpression of OCT-1 gene is a biomarker of adverse prognosis for diffuse large B-cell lymphoma (DLBCL): data from a retrospective cohort of 77 Brazilian patients
title_full Overexpression of OCT-1 gene is a biomarker of adverse prognosis for diffuse large B-cell lymphoma (DLBCL): data from a retrospective cohort of 77 Brazilian patients
title_fullStr Overexpression of OCT-1 gene is a biomarker of adverse prognosis for diffuse large B-cell lymphoma (DLBCL): data from a retrospective cohort of 77 Brazilian patients
title_full_unstemmed Overexpression of OCT-1 gene is a biomarker of adverse prognosis for diffuse large B-cell lymphoma (DLBCL): data from a retrospective cohort of 77 Brazilian patients
title_short Overexpression of OCT-1 gene is a biomarker of adverse prognosis for diffuse large B-cell lymphoma (DLBCL): data from a retrospective cohort of 77 Brazilian patients
title_sort overexpression of oct 1 gene is a biomarker of adverse prognosis for diffuse large b cell lymphoma dlbcl data from a retrospective cohort of 77 brazilian patients
topic Diffuse large B-cell lymphoma (DLBCL)
OCT-1 gene
BCL-2 gene
Prognosis
Immunochemotherapy
url http://link.springer.com/article/10.1186/s12885-020-07553-2
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