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), Av. Dr. Enéas Carvalho de Aguiar, 155, Cerqueira César, São Paulo, Brazil.
Department of Molecular Biology, Pró-Sangue Foundation, Sao Paulo Blood Bank, São Paulo, Brazil.
BMC Cancer. 2020 Oct 29;20(1):1041. doi: 10.1186/s12885-020-07553-2.
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.
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.
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).
In this study, we showed that overexpression of OCT1 gene was an independent prognostic factor of adverse outcomes in DLBCL.
OCT-1 基因是 B 淋巴细胞分化的 POU-homeodomain 家族转录调节因子之一，通过控制 B 细胞特异性基因的表达来控制 B 细胞的分化。BCL-2 基因是细胞凋亡的有力抑制剂，在 B 细胞分化为生发中心时是必不可少的。这些基因可能在弥漫性大 B 细胞淋巴瘤 (DLBCL) 中表达，但 BCL-2 在其预后中的作用一直存在争议，而 OCT-1 尚未经过测试。
在这项研究中，我们旨在研究在单中心接受免疫化学治疗的真实世界中，OCT-1 和 BCL-2 表达对 DLBCL 的预后影响。在 98 例 DLBCL 患者中，有 78.5%（77/98）可获得 BCL-2 和 OCT-1 基因，从福尔马林固定石蜡包埋样本中分离 RNA 用于实时定量 PCR。根据中位数将基因表达的数值转换为分类变量。
队列的中位年龄为 54.5 岁（15-84 岁），49 名（50%）为男性，38/77（49.4%）和 40/77（51.9%）分别表达 OCT-1 和 BCL-2 表达≥中位数。所有患者的总缓解率（ORR）为 68.4%（67/98），64/98（65.3%）患者获得完全缓解，3/98（3.1%）患者部分缓解，而 6/98（6.1%）患者为原发性耐药。中位随访时间为 3.77 年（95%CI：3.2-4.1），总生存率（OS）为 5.43 年（95%CI：2.2-NR），无进展生存率（PFS）为 5.15 年（95%CI：2.9-NA）。OCT-1≥中位数在单因素分析中与较短的 OS 相关（p=0.013；[HR]2.450，95%CI：1.21-4.96）和 PFS（p=0.019；[HR]2.270，95%CI：1.14-4.51），BCL-2 基因过表达与较差的 PFS 相关（p=0.043，[HR]2.008，95%CI：1.02-3.95）。在多因素分析中，OCT-1 过表达与不良 PFS 相关（p=0.035，[HR]2.22，95%CI：1.06-4.67）。
在这项研究中，我们表明 OCT1 基因的过表达是 DLBCL 不良预后的独立预后因素。
