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

Abstract

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin’s lymphoma (NHL), which can involve various types of mature B-cells. The incidence of DLBCL has been increased, additional research is required to identify novel and effective prognostic and therapeutic molecules. Fc receptor-like 1 (FCRL1) act 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 not completely identified. Methods In this study, the expression levels of FCRL1 was 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 expression levels of BCL-2, BID, BAX, intracellular signaling pathway PI3K/p-Akt, and p65 nuclear factor-kappa B (NF-κB) in B-cells of DLBCL. Results Statistical analysis revealed higher levels of FCRL1 expression in B-cells of DLBCL patients compared to HCs at both protein and mRNA levels. A positive correlation observed between the expression of FCRL1 with 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 B-cells of DLBCL patients. The levels of p65 NF-κB and PI3K/p-Akt expression markedly reduced after knockdown of FCRL1 expression. Conclusions These results suggested FCRL1 as a potential novel biomarker for prognosis and/or a possible effective therapeutic target for treatment of patients with DLBCL.