Zhang Jing, Gu Yan, Guan Jia-Heng, Wu Xue, Chen Bao-An
School of Medicine, Southeast University,Nanjing 210009, Jiangsu Province, China.
Department of Hematology, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Apr;33(2):393-406. doi: 10.19746/j.cnki.issn.1009-2137.2025.02.013.
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.
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 knockdown. Differential expression gene (DEG) was examined based on the transcriptomes.
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 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 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 high and low expression groups, and the was identified as the down-stream effector of . Inhibiting the function of XPO1 or reducing its expression can significantly decrease the expression of Conclusion: XPO1 is highly expressed in DLBCL, which is associated with poor prognosis. The oncogenic roles of the new signaling are identified in DLBCL and XPO1 inhibitor may be a potential option for newly-diagnosed DLBCL patients.
探讨XPO1在新诊断的成人弥漫性大B细胞淋巴瘤（DLBCL）中的表达及临床意义，并进一步研究其功能机制。
对93例DLBCL患者和30例反应性淋巴组织增生患者进行XPO1表达的免疫组织化学检测。构建风险模型以寻找DLBCL患者中与生存相关的基因。进行细胞增殖、凋亡和细胞周期检测，以探讨XPO1抑制剂（KPT-8602）和基因敲低的作用。基于转录组检测差异表达基因（DEG）。
DLBCL患者中XPO1的表达高于对照组。与XPO1低表达组相比，XPO1高表达组预后较差。构建的风险模型表明，核质转运途径（NTP）中的14个基因可能是DLBCL不良预后的潜在预测标志物。此外，KPT-8602以及基因敲低可抑制两种DLBCL细胞系Farage和SU-DHL-4的细胞增殖，促进凋亡并诱导细胞周期停滞。基于DLBCL数据集中的基因表达谱，将患者分为高表达组和低表达组，并确定为的下游效应物。抑制XPO1的功能或降低其表达可显著降低的表达。结论：XPO1在DLBCL中高表达，与预后不良相关。在DLBCL中确定了新的信号传导的致癌作用，XPO1抑制剂可能是新诊断的DLBCL患者的潜在选择。
