Proliferative, Pro-inflammatory, and Angiogenesis Regulator Gene Expression Profile Defines Prognosis in Different Histopathological Subtypes of Nodal Peripheral T-cell Lymphoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2019 Sep 10

PMID 31497245

Citations 1

Authors

Luis Alberto de Padua Covas Lage

Debora Levy

Flavia Dias Xavier

Diego Candido Reis

Renata de Oliveira Costa

Marianne Castro Goncalves

Vanderson Rocha

Maria Claudia Nogueira Zerbini

Juliana Pereira

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Tumor mutation burden involving epigenetic regulatory genes and the RhoA GTPase predicts overall survival in nodal mature T-cell lymphomas.

Lage L, Culler H, Barreto G, Reichert C, Levy D, Costa R Clin Epigenetics. 2022; 14(1):180.

PMID: 36536430 PMC: 9764541. DOI: 10.1186/s13148-022-01395-4.

References

Boonstra P, Polk A, Brown N, Hristov A, Bailey N, Kaminski M . A single center phase II study of ixazomib in patients with relapsed or refractory cutaneous or peripheral T-cell lymphomas. Am J Hematol. 2017; 92(12):1287-1294. PMC: 6116510. DOI: 10.1002/ajh.24895. View

Gascoyne R, Aoun P, Wu D, Chhanabhai M, Skinnider B, Greiner T . Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma. Blood. 1999; 93(11):3913-21. View

Adams J . The development of proteasome inhibitors as anticancer drugs. Cancer Cell. 2004; 5(5):417-21. DOI: 10.1016/s1535-6108(04)00120-5. View

. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood. 1997; 89(11):3909-18. View

Gilmore T, Herscovitch M . Inhibitors of NF-kappaB signaling: 785 and counting. Oncogene. 2006; 25(51):6887-99. DOI: 10.1038/sj.onc.1209982. View

Zhao W, Mourah S, Mounier N, Leboeuf C, Daneshpouy M, Legres L . Vascular endothelial growth factor-A is expressed both on lymphoma cells and endothelial cells in angioimmunoblastic T-cell lymphoma and related to lymphoma progression. Lab Invest. 2004; 84(11):1512-9. DOI: 10.1038/labinvest.3700145. View

Belder N, Coskun O, Doganay Erdogan B, Ilk O, Savas B, Ensari A . From RNA isolation to microarray analysis: Comparison of methods in FFPE tissues. Pathol Res Pract. 2016; 212(8):678-85. DOI: 10.1016/j.prp.2015.11.008. View

DAmore F, Relander T, Lauritzsen G, Jantunen E, Hagberg H, Anderson H . Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012; 30(25):3093-9. DOI: 10.1200/JCO.2011.40.2719. View

STEIN H, Foss H, Durkop H, Marafioti T, Delsol G, Pulford K . CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood. 2000; 96(12):3681-95. View

10.

Bustin S, Benes V, Garson J, Hellemans J, Huggett J, Kubista M . The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009; 55(4):611-22. DOI: 10.1373/clinchem.2008.112797. View

11.

Schmitz N, Trumper L, Ziepert M, Nickelsen M, Ho A, Metzner B . Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group. Blood. 2010; 116(18):3418-25. DOI: 10.1182/blood-2010-02-270785. View

12.

ANDERSON J, Armitage J, Weisenburger D . Epidemiology of the non-Hodgkin's lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin's Lymphoma Classification Project. Ann Oncol. 1998; 9(7):717-20. DOI: 10.1023/a:1008265532487. View

13.

Schmid J, Birbach A . IkappaB kinase beta (IKKbeta/IKK2/IKBKB)--a key molecule in signaling to the transcription factor NF-kappaB. Cytokine Growth Factor Rev. 2008; 19(2):157-65. DOI: 10.1016/j.cytogfr.2008.01.006. View

14.

Vose J, Armitage J, Weisenburger D . International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008; 26(25):4124-30. DOI: 10.1200/JCO.2008.16.4558. View

15.

Cheson B, Fisher R, Barrington S, Cavalli F, Schwartz L, Zucca E . Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 32(27):3059-68. PMC: 4979083. DOI: 10.1200/JCO.2013.54.8800. View

16.

Trigos A, Pearson R, Papenfuss A, Goode D . How the evolution of multicellularity set the stage for cancer. Br J Cancer. 2018; 118(2):145-152. PMC: 5785747. DOI: 10.1038/bjc.2017.398. View

17.

Feinman R, Siegel D, Berenson J . Regulation of NF-kB in multiple myeloma: therapeutic implications. Clin Adv Hematol Oncol. 2005; 2(3):162-6. View

18.

Demchenko Y, Kuehl W . A critical role for the NFkB pathway in multiple myeloma. Oncotarget. 2010; 1(1):59-68. PMC: 2947827. DOI: 10.18632/oncotarget.109. View

19.

Sibon D, Fournier M, Briere J, Lamant L, Haioun C, Coiffier B . Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials. J Clin Oncol. 2012; 30(32):3939-46. DOI: 10.1200/JCO.2012.42.2345. View

20.

Falini B, Pileri S, Zinzani P, Carbone A, Zagonel V, Verhoef G . ALK+ lymphoma: clinico-pathological findings and outcome. Blood. 1999; 93(8):2697-706. View