Abstract
BackgroundOCT-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.MethodsIn 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.ResultsCohort 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).ConclusionIn this study, we showed that overexpression of OCT1 gene was an independent prognostic factor of adverse outcomes in DLBCL.
Highlights
Octamer transcription factor 1 (OCT-1) gene is a member of the POU-homeodomain family of transcriptional regulators of Blymphocyte differentiation by controlling expression of B-cell specific genes
In this study, we showed that overexpression of Octamer transcription factor 1 (OCT1) gene was an independent prognostic factor of adverse outcomes in Diffuse large B-cell lymphoma (DLBCL)
More intensive regimens combining additional antineoplastic agents given in a continuous infusion such as DA-REPOCH have improved the overall survival of mediastinal primary lymphoma (PMBCL) and high grade lymphoma with B-cell lymphoma 2 gene (BCL-2) and MYC genes rearrangement with or without BCL-6 rearrangement [4, 5]
Summary
OCT-1 gene is a member of the POU-homeodomain family of transcriptional regulators of Blymphocyte 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. The addition of the monoclonal antibody anti-CD20 to the CHOP regimen provided significant improvement in the survival of DLBCL patients [3, 6, 7]. The determination of the biological heterogeneity of DLBCL to improve risk prediction and design targeted therapies for poor prognosis is an urgent need
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