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细胞周期蛋白依赖性激酶1(CDK1)表达在弥漫性大B细胞淋巴瘤中的预后意义

Prognostic significance of CDK1 expression in diffuse large B-Cell lymphoma.

作者信息

Chen Qiuni, Xu Lei, Lu Chuanyang, Xue Yujie, Gong Xue, Shi Yuye, Wang Chunling, Yu Liang

机构信息

Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, 223300, Jiangsu Province, PR China.

Key Laboratory of Hematology, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, PR China.

出版信息

BMC Cancer. 2025 Jan 7;25(1):20. doi: 10.1186/s12885-024-13388-y.

Abstract

BACKGROUND

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adult, characterized by uncontrolled cell proliferation and strong aggressiveness. Previous studies have found that cyclin-dependent kinase 1(CDK1) are related to tumor growth and metastasis. However, the role of CDK1 in DLBCL is exclusive. This study investigated the clinical implications and expression of CDK1 in DLBCL.

METHODS

Gene expression data for healthy subjects were sourced from the Genotype-Tissue Expression repository. Clinical details and survival statistics of patients with DLBCL were obtained from the Gene Expression Omnibus archive (GSE10846). Patients were categorized based on CDK1 expression levels, and differences in clinical outcomes between the groups were examined. Univariate and multivariate Cox regression analyses were used to ascertain whether CDK1 expression independently predicted DLBCL prognosis. The protein expression of CDK1 was gauged by immunohistochemistry. Additionally, we investigated the effect of CDK1 inhibition on DLBCL cell growth and death using the Cell Counting Kit-8 and flow cytometry.

RESULTS

In the control group, CDK1 expression was predominantly observed in the hematopoietic and reproductive systems. CDK1 levels in patients with DLBCL were notably elevated compared with those in controls. Significant differences were noted in the lactate dehydrogenase ratio and overall survival based on CDK1 expression. Statistical analyses confirmed that CDK1 was an independent predictor of DLBCL outcomes. Elevated CDK1 protein levels were observed in a significant number of DLBCL samples, in contrast to normal lymph node samples from individuals without lymphoma. The inhibitor Ro-3306 curtails DLBCL cell growth and enhances cell death in vitro.

CONCLUSIONS

Elevated CDK1 levels are correlated with poor prognosis in patients with DLBCL.

摘要

背景

弥漫性大B细胞淋巴瘤(DLBCL)是成人中最常见的淋巴瘤,其特征为细胞增殖失控且侵袭性强。既往研究发现细胞周期蛋白依赖性激酶1(CDK1)与肿瘤生长和转移有关。然而,CDK1在DLBCL中的作用尚不明确。本研究探讨了CDK1在DLBCL中的临床意义及表达情况。

方法

健康受试者的基因表达数据来源于基因型-组织表达库。DLBCL患者的临床细节和生存统计数据来自基因表达综合数据库(GSE10846)。根据CDK1表达水平对患者进行分类,并检查各组间临床结局的差异。采用单因素和多因素Cox回归分析确定CDK1表达是否能独立预测DLBCL的预后。通过免疫组织化学检测CDK-1的蛋白表达。此外,我们使用细胞计数试剂盒-8和流式细胞术研究了CDK1抑制对DLBCL细胞生长和死亡的影响。

结果

在对照组中,主要在造血和生殖系统中观察到CDK1表达。与对照组相比,DLBCL患者的CDK1水平显著升高。基于CDK1表达,乳酸脱氢酶比值和总生存期存在显著差异。统计分析证实CDK1是DLBCL结局的独立预测因子。与无淋巴瘤个体的正常淋巴结样本相比,在大量DLBCL样本中观察到CDK1蛋白水平升高。抑制剂Ro-3306在体外可抑制DLBCL细胞生长并增强细胞死亡。

结论

CDK1水平升高与DLBCL患者的不良预后相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e8c/11705832/f21dc54fd269/12885_2024_13388_Fig1_HTML.jpg

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