Proliferative, pro-inflammatory, and angiogenesis regulator gene expression profile defines prognosis in different histopathological subtypes of nodal peripheral T-cell lymphoma
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Luís Alberto de Pádua Covas Lage1, Débora Levy2, Flávia Dias Xavier3, Diego Cândido Reis4, Renata de Oliveira Costa5, Marianne Castro Gonçalves6, Vanderson Rocha1,7, Maria Cláudia Nogueira Zerbini6 and Juliana Pereira1
1 Department of Hematology, Hemotherapy and Cell Therapy, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
2 Laboratory of Medical Investigation in Genetics and Molecular Hematology (LIM-31), Universidade de São Paulo, SãoPaulo, Brazil
3 Department of Hematology and Hemotherapy, Faculdade de Medicina da Universidade de Brasília, Brasília, Brazil
4 Medical Sciences Discipline, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
5 Department of Hematology and Hemotherapy Discipline, Faculdade de Ciências Médicas de Santos/Centro Universitário Lusíada, Santos, Brazil
6 Departamento of Pathology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
7 President Fundação Pró-Sangue, Churchill Hospital, Oxford University, Oxford, UK
|Luís Alberto de Pádua Covas Lage,||email:||[email protected]|
Keywords: peripheral T-cell lymphoma; gene expression analysis; cell cycle regulation; inflammation; prognosis
Received: January 10, 2019 Accepted: June 05, 2019 Published: August 27, 2019
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 (CCNA2, TOP2A, and CHEK1), pro-inflammatory activity (NFkB1 and IKBkB), and angiogenesis (VEGF1) 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; p = 0.007) were associated with worse OS for all the cohort of nodal PTCL (HR 1.418; p = 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.
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