Clinical Significance of XPO1 High Expression in Diffuse Large B-Cell Lymphoma and Its Mechanism.
10.19746/j.cnki.issn.1009-2137.2025.02.013
- Author:
Jing ZHANG
1
;
Yan GU
2
;
Jia-Heng GUAN
1
;
Xue WU
2
;
Bao-An CHEN
1
Author Information
1. School of Medicine, Southeast University,Nanjing 210009, Jiangsu Province, China.
2. Department of Hematology, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China.
- Publication Type:Journal Article
- Keywords:
diffuse large B-cell lymphoma;
XPO1;
XPO1 inhibitor;
MYBL1;
prognosis
- MeSH:
Humans;
Lymphoma, Large B-Cell, Diffuse/pathology*;
Exportin 1 Protein;
Karyopherins/metabolism*;
Receptors, Cytoplasmic and Nuclear/metabolism*;
Cell Proliferation;
Apoptosis;
Prognosis;
Cell Line, Tumor;
Clinical Relevance
- From:
Journal of Experimental Hematology
2025;33(2):393-406
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the expression and clinical significance of XPO1 in newly diagnosed adult diffuse large B-cell lymphoma (DLBCL), and further investigate its functional mechanism.
METHODS:Immunohistochemical testing was conducted for XPO1 expression in 93 cases of DLBCL and 30 cases of reactive lymphoid hyperplasia. A risk model was construed to find survival related genes in DLBCL patients. Cell proliferation, apoptosis, and cell cycle assays were performed to explore the effect of XPO1 inhibitor (KPT-8602) and XPO1 knockdown. Differential expression gene (DEG) was examined based on the transcriptomes.
RESULTS:The expression of XPO1 in DLBCL patients was higher than that of the controls. Compared with XPO1 low-expression group, XPO1 high-expression group had a worse prognosis. The constructed risk model indicated that XPO1 and 14 genes in nucleocytoplasmic transport pathway (NTP) might be potential prediction marker of adverse outcome in DLBCL. Moreover, KPT-8602 as well as the XPO1 knockdown could inhibit cell proliferation, promote apoptosis, and induce cell cycle arrest in two DLBCL cell lines, Farage and SU-DHL-4. Based on the gene expression profiling in the datasets of DLBCL, patients were classified into XPO1 high and XPO1 low expression groups, and the MYBL1 was identified as the down-stream effector of XPO1. Inhibiting the function of XPO1 or reducing its expression can significantly decrease the expression of MYBL1 Conclusion: XPO1 is highly expressed in DLBCL, which is associated with poor prognosis. The oncogenic roles of the new XPO1/MYBL1 signaling are identified in DLBCL and XPO1 inhibitor may be a potential option for newly-diagnosed DLBCL patients.
