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

Abstract

BackgroundDiffuse 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 signi cance and prognosis value of FCRL1 in DLBCL not completely identi ed. MethodsIn 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 ow 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. ResultsStatistical 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 signi cantly 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. ConclusionsThese results suggested FCRL1 as a potential novel biomarker for prognosis and/or a possible effective therapeutic target for treatment of patients with DLBCL.

FCRL1 immunoregulation in B cell development and malignancy

“…Cell cycle analysis by propidium iodide staining showed that frequencies of G2/M cells were reduced, but sub-G1 and G1 cells were increased in hFCRL1-depleted cells after 72 hours, indicating higher levels of apoptosis. Although the rigor of these FCRL1 deficiency studies ( 108 , 109 ), with respect to targeting efficiency and numbers of replicate experiments are somewhat unclear, the results are consistent with observations of positive roles for FCRL1 in B cell proliferation and survival.…”

“…These studies did not assess the impact of BCR stimulation, but 48 hours after FCRL1 knockdown, transcripts encoding the anti-apoptotic gene B cell lymphoma 2 ( BCL2) were lower, whereas the pro-apoptotic BH3 interacting-domain death agonist ( BID) and BCL2-associated X protein ( BAX) genes rose. A follow up report using this shRNA approach in primary DLBCL patient samples indicated similar defects in proliferation and apoptosis ( 109 ). Cell cycle analysis by propidium iodide staining showed that frequencies of G2/M cells were reduced, but sub-G1 and G1 cells were increased in hFCRL1-depleted cells after 72 hours, indicating higher levels of apoptosis.…”

Natural killer cell‐based signature: Prognostic analysis in head and neck squamous cell carcinoma

“…Cheminant et al found that KIR3DL2 is a underlying target of acute adult T‐cell leukemia 45 . Meanwhile, FCRL1 was also reported as a possible prognostic marker for diffuse large B‐cell lymphoma 46 . ZNF541 was discovered to be related to the radiosensitivity of breast cancer 47 .…”

Association between plasma proteome and glioma: A two-sample Mendelian randomization analysis

“…Studies have shown that it is a poor prognostic marker for non-small cell lung cancer (42), but there is currently a lack of research on its relationship with glioma. Fc receptor-like protein (FCRL) is a marker for multiple B-cell tumors (43,44), but its relationship with non-lymphatic system tumors such as glioma is still unclear, which requires further research.…”