Fc 受体样蛋白 1（FCRL1）是弥漫性大 B 细胞淋巴瘤预后的新型生物标志物和潜在治疗靶点。

Fc receptor-like 1 (FCRL1) is a novel biomarker for prognosis and a possible therapeutic target in diffuse large B-cell lymphoma.

机构信息

School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran.

Division of Medical Biotechnology, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Mol Biol Rep. 2023 Feb;50(2):1133-1145. doi: 10.1007/s11033-022-08104-7. Epub 2022 Nov 21.

DOI:10.1007/s11033-022-08104-7

PMID:36409389

Abstract

BACKGROUND

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma, which can involve various types of mature B-cells. Considering that the incidence of DLBCL has increased, additional research is required to identify novel and effective prognostic and therapeutic molecules. Fc receptor-like 1 (FCRL1) acts as an activation co-receptor of human B-cells. Aberrant expression of this molecule has been reported in a number of B-cell-related disorders. Moreover, the clinical significance and prognosis value of FCRL1 in DLBCL are not completely identified.

METHODS

In this study, the expression levels of FCRL1 were determined in thirty patients with DLBCL and 15 healthy controls (HCs). In addition, the correlation between FCRL1 expressions with clinicopathological variables of DLBCL patients were examined. Then, the potential roles of FCRL1 in proliferation, apoptosis, and cell cycle distribution of B-cells from DLBCL patients were determined using flow cytometry analysis, after knockdown of this marker using retroviral short hairpin RNA interference. Quantitative real time-PCR, western blotting, and enzyme-linked immunosorbent assay were also used to identify the possible effects of FCRL1 knockdown on the expression levels of BCL-2, BID, BAX, intracellular signaling pathway PI3K/p-Akt, and p65 nuclear factor-kappa B (NF-κB) in the B-cells of DLBCL.

RESULTS

Statistical analysis revealed higher levels of FCRL1 expression in the B-cells of DLBCL patients compared to HCs at both protein and mRNA levels. A positive correlation was observed between the FCRL1 expression and some clinicopathological parameters of DLBCL patients. In addition, FCRL1 knockdown significantly decreased cell proliferation and stimulated apoptosis as well as G1 cell cycle arrest in the B-cells of DLBCL patients. The levels of p65 NF-κB and PI3K/p-Akt expressions were markedly reduced after knockdown of FCRL1 expression.

CONCLUSIONS

These results suggested that FCRL1 could be a potential novel biomarker for prognosis and/or a possible effective therapeutic target for treatment of patients with DLBCL.

摘要

背景

弥漫性大 B 细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤亚型，可涉及各种类型的成熟 B 细胞。鉴于 DLBCL 的发病率有所增加，需要开展更多的研究来鉴定新的有效的预后和治疗分子。Fc 受体样 1（FCRL1）作为人类 B 细胞的激活共受体。已有研究报道该分子在多种 B 细胞相关疾病中表达异常。此外，FCRL1 在 DLBCL 中的临床意义和预后价值尚不完全明确。

方法

本研究检测了 30 例 DLBCL 患者和 15 例健康对照者（HCs）的 FCRL1 表达水平，并分析了 FCRL1 表达与 DLBCL 患者临床病理变量的相关性。然后，通过逆转录病毒短发夹 RNA 干扰敲低该标志物，应用流式细胞术分析了 FCRL1 对 DLBCL 患者 B 细胞增殖、凋亡和细胞周期分布的潜在作用。还应用实时定量 PCR、Western blot 和酶联免疫吸附试验鉴定了 FCRL1 敲低对 DLBCL 患者 B 细胞中 BCL-2、BID、BAX、细胞内信号通路 PI3K/p-Akt 和核因子-κB（NF-κB）p65 表达水平的可能影响。

结果

统计分析显示，DLBCL 患者 B 细胞中的 FCRL1 蛋白和 mRNA 水平均高于 HCs。FCRL1 表达与 DLBCL 患者的某些临床病理参数呈正相关。此外，FCRL1 敲低可显著降低 DLBCL 患者 B 细胞的增殖，刺激其凋亡，并诱导 G1 期细胞周期阻滞。FCRL1 表达下调后，p65 NF-κB 和 PI3K/p-Akt 表达水平明显降低。