de Pádua Covas Lage Luís Alberto, Levy Débora, Xavier Flávia Dias, Reis Diego Cândido, de Oliveira Costa Renata, Gonçalves Marianne Castro, Rocha Vanderson, Zerbini Maria Cláudia Nogueira, Pereira Juliana
Department of Hematology, Hemotherapy and Cell Therapy, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
Laboratory of Medical Investigation in Genetics and Molecular Hematology (LIM-31), Universidade de São Paulo, SãoPaulo, Brazil.
Oncotarget. 2019 Aug 27;10(50):5136-5151. doi: 10.18632/oncotarget.27098.
Nodal peripheral T-cell lymphoma (PTCL) is an aggressive and heterogeneous malignancy with poor prognosis. We studied the prognostic impact of the expression profile of genes related to cell proliferation (, , and ), pro-inflammatory activity ( and ), and angiogenesis () in nodal PTCL outcomes, as well as the ability of this genomic panel to discriminate different histological subtypes. We investigated the relative expression of regulator genes in 63 nodal PTCL patients. CCNA2, TOP2A, CHEK1, and NF-kB1 proteins were also assessed by immunohistochemistry. The median patient age was 47 years, 57.1% were male, 34.9% were diagnosed with PTCL-NOS, 28.6% with ALK-/ALCL, 22.2% with ALK+/ALCL, and 14.3% with AITL. The proliferative genes were associated with worse 3-year OS and PFS in PTCL-NOS and better 3-year PFS in ALK-/ALCL. Expression of CCNA2≥median and overexpression of CHEK1 protein (HR 3.793; = 0.007) were associated with worse OS for all the cohort of nodal PTCL (HR 1.418; = 0.001). The genomic expression profile tested in this study was not able to discriminate the different subtypes of nodal PTCL, although it showed a distinct prognostic significance between PTCL-NOS and ALCL-ALK. Overexpression of the CCNA2 gene and CHEK1 protein were associated with poor prognosis in the total nodal PTCL cohort.
结外外周T细胞淋巴瘤（PTCL）是一种侵袭性且异质性的恶性肿瘤，预后较差。我们研究了与细胞增殖（CCNA2、TOP2A和CHEK1）、促炎活性（NF-κB1和IL-6）以及血管生成（VEGF）相关基因的表达谱对结外PTCL预后的影响，以及该基因组检测区分不同组织学亚型的能力。我们调查了63例结外PTCL患者中调节基因的相对表达。还通过免疫组织化学评估了CCNA2、TOP2A、CHEK1和NF-κB1蛋白。患者中位年龄为47岁，57.1%为男性，34.9%被诊断为PTCL-NOS，28.6%为ALK-/间变大细胞淋巴瘤（ALCL），22.2%为ALK+/ALCL，14.3%为血管免疫母细胞性T细胞淋巴瘤（AITL）。增殖基因与PTCL-NOS患者较差的3年总生存期（OS）和无进展生存期（PFS）相关，与ALK-/ALCL患者较好的3年PFS相关。CCNA2表达≥中位数以及CHEK1蛋白过表达（风险比[HR] 3.793；P = 0.007）与所有结外PTCL队列较差的OS相关（HR 1.418；P = 0.001）。本研究中检测的基因组表达谱无法区分结外PTCL的不同亚型，尽管它在PTCL-NOS和ALK-ALCL之间显示出明显的预后意义。CCNA2基因和CHEK1蛋白过表达与整个结外PTCL队列的不良预后相关。
