[Expression of CDK6 and FOXM1 in peripheral T-cell lymphoma and their significance]

Zhonghua Bing Li Xue Za Zhi. 2020 Jun 8;49(6):594-600. doi: 10.3760/cma.j.cn112151-20191104-00710.
[Article in Chinese]

Abstract

Objective: To investigate the expression of CDK6 and FOXM1 in peripheral T-cell lymphoma (PTCL), and its correlation with clinicopathologic features and patient prognosis. Methods: The Oncomine was used for data mining and analyzing the expression levels of CDK6 and FOXM1 in PTCL. Immunohistochemistry (IHC) of EnVision method was used to detect the expression of CDK6 and FOXM1 proteins in 166 cases of PTCL diagnosed at Shanxi Provincial Cancer Hospital from January 2016 to December 2018, and 30 cases of lymph node with reactive hyperplasia as control. Results: Among the PTCL patients, 104 were male and 62 were female, aged from 3 to 85 years, with an average age of 53 years. Analyses of the Oncomine 4.5 database showed that mRNA expression of CDK6 and FOXM1 in PTCL tissues was significantly higher than that in normal tissue (P<0.05). IHC staining showed the positive rates of CDK6 and FOXM1 proteins in PTCL tissues were 27.7% (46/166) and 80.7% (134/166), respectively. The expression was mainly present in the nuclei of tumor cells, showing a diffuse, strongly positive pattern. The positive rates of CDK6 and FOXM1 proteins among the 30 cases of lymph-node reactive hyperplasia were 0 (0/30) and 30% (9/30), respectively. The expression of FOXM1 was mainly found in the lymphoid follicle germinal center, and not present in the T-zone cells. CDK6 protein, FOXM1 protein and the co-expression of CDK6 and FOXM1 proteins in PTCL were associated with higher Ann Arbor staging and international prognostication index score (P<0.05), and inversely associated with overall survival (P<0.05). Meanwhile, CDK6 protein expression was positively correlated with FOXM1 protein expression (P<0.05). Conclusions: CDK6 and FOXM1 may be new targets for the diagnosis and treatment of PTCL. The overexpression of CDK6 may lead to enhanced function of the transcription factor FOXM1, while the overexpression of CDK6 and FOXM1 also promotes the development and progression of PTCL.

目的: 研究CDK6和FOXM1在外周T细胞淋巴瘤(peripheral T-cell lymphoma,PTCL)组织中的表达情况,探讨其与患者临床病理特征及预后的关系。 方法: 利用Oncomine 4.5数据库分析PTCL组织中CDK6和FOXM1的表达水平;收集山西省肿瘤医院病理科2006年1月至2018年12月诊断的166例PTCL患者病历资料及存档石蜡标本,应用免疫组织化学(IHC)EnVision法检测166例PTCL组织中CDK6和FOXM1的蛋白表达水平,并以30例淋巴结反应性增生组织作为对照。 结果: 男性104例,女性62例,年龄3~85岁,平均年龄53岁。Oncomine 4.5数据库中的数据显示,PTCL组织中CDK6和FOXM1 mRNA的表达明显高于正常组织(P<0.05)。PTCL组织中CDK6和FOXM1蛋白阳性表达率分别为27.7%(46/166)与80.7%(134/166),主要见于肿瘤细胞的细胞核,呈弥漫强阳性表达;在30例淋巴结反应性增生组织中CDK6和FOXM1蛋白阳性表达率分别为0(0/30)和30.0%(9/30),主要表达于淋巴滤泡生发中心,T区细胞不表达。PTCL组织中CDK6、FOXM1及两者蛋白共表达均与患者的Ann Arbor分期、国际预后指数(IPI)评分呈正相关(P<0.05),与患者总生存期呈负相关(P<0.05)。CDK6蛋白表达与FOXM1蛋白表达呈正相关(P<0.05)。 结论: CDK6、FOXM1可能是诊断及治疗PTCL的新靶点。CDK6的过表达可能导致转录因子FOXM1功能增强,且CDK6及FOXM1的过表达作为不利因素促进了PTCL的发生发展。.

Keywords: Immunohistochemistry; Peripheral T-cell lymphoma; Prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Cyclin-Dependent Kinase 6 / metabolism*
  • Female
  • Forkhead Box Protein M1 / metabolism*
  • Humans
  • Immunohistochemistry
  • Lymph Nodes
  • Lymphoma, T-Cell, Peripheral*
  • Male
  • Middle Aged
  • Prognosis
  • Young Adult

Substances

  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6