Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia
Autor(a) principal: | |
---|---|
Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.1590/s2175-97902022e19332 http://hdl.handle.net/1843/61335 https://orcid.org/0000-0002-3944-7235 |
Resumo: | Chronic lymphocytic leukemia (CLL) is a blood cancer characterized by the accumulation of clonal B-lymphocytes. This study evaluated the mRNA gene expression of miR-15a, miR-16- 1, ZAP-70, and Ang-2 by qPCR, as well as the plasma levels of Bcl-2 by Elisa immunoassay, in CLL patients and healthy controls. Significant differences were observed when comparing patients and controls regarding miR-15a (p < 0.001), miR-16-1 (p < 0.001) mRNA, Ang-2 gene expression, and Bcl-2 plasma levels (p < 0.001). When stratified by risk, differences were maintained with a significantly reduced expression in high-risk patients. A positive correlation was observed between miR-15a and platelets (R2 = 0.340; p = 0.009) as well as between Bcl-2 and leukocytes (R2 = 0.310; p = 0.019). Conversely, negative correlations were observed between ZAP-70 and platelets (R2 = - 0.334; p = 0.011), between miR-15a and lymphocytes (R2 = - 0.376; p = 0.004), as well as between miR-16-and lymphocytes (R2 = - 0.515; p = 0.00004). The data suggest that a reduction in miR-15a and miR-16-1 expressions, in addition to an overexpression of Bcl-2, are associated with the reduction in apoptosis and, consequently, to a longer survival of lymphocytes, thus contributing to lymphocyte accumulation and aggravation of the disease. By contrast, Ang-2 expression was significantly higher in A than in B + C Binet groups. This context leads to the speculation that this biomarker should be investigated in more robust studies within populations with a still relevantly indolent form of the disease in an attempt to identify those patients with a greater potential for an aggravation of the disease. |
id |
UFMG_14aeff1d385e4bb3ad8696eae0f55a2b |
---|---|
oai_identifier_str |
oai:repositorio.ufmg.br:1843/61335 |
network_acronym_str |
UFMG |
network_name_str |
Repositório Institucional da UFMG |
repository_id_str |
|
spelling |
2023-11-23T22:45:05Z2023-11-23T22:45:05Z202258https://doi.org/10.1590/s2175-97902022e193322175-9790http://hdl.handle.net/1843/61335https://orcid.org/0000-0002-3944-7235Chronic lymphocytic leukemia (CLL) is a blood cancer characterized by the accumulation of clonal B-lymphocytes. This study evaluated the mRNA gene expression of miR-15a, miR-16- 1, ZAP-70, and Ang-2 by qPCR, as well as the plasma levels of Bcl-2 by Elisa immunoassay, in CLL patients and healthy controls. Significant differences were observed when comparing patients and controls regarding miR-15a (p < 0.001), miR-16-1 (p < 0.001) mRNA, Ang-2 gene expression, and Bcl-2 plasma levels (p < 0.001). When stratified by risk, differences were maintained with a significantly reduced expression in high-risk patients. A positive correlation was observed between miR-15a and platelets (R2 = 0.340; p = 0.009) as well as between Bcl-2 and leukocytes (R2 = 0.310; p = 0.019). Conversely, negative correlations were observed between ZAP-70 and platelets (R2 = - 0.334; p = 0.011), between miR-15a and lymphocytes (R2 = - 0.376; p = 0.004), as well as between miR-16-and lymphocytes (R2 = - 0.515; p = 0.00004). The data suggest that a reduction in miR-15a and miR-16-1 expressions, in addition to an overexpression of Bcl-2, are associated with the reduction in apoptosis and, consequently, to a longer survival of lymphocytes, thus contributing to lymphocyte accumulation and aggravation of the disease. By contrast, Ang-2 expression was significantly higher in A than in B + C Binet groups. This context leads to the speculation that this biomarker should be investigated in more robust studies within populations with a still relevantly indolent form of the disease in an attempt to identify those patients with a greater potential for an aggravation of the disease.A leucemia linfocítica crônica (LLC) é um câncer do sangue caracterizado pelo acúmulo de linfócitos B clonais. Este estudo avaliou a expressão gênica de mRNA de miR-15a, miR-16-1, ZAP-70 e Ang-2 por qPCR, bem como os níveis plasmáticos de Bcl-2 por imunoensaio Elisa, em pacientes com LLC e controles saudáveis. Diferenças significativas foram observadas na comparação entre pacientes e controles em relação ao mRNA do miR-15a (p < 0,001), miR-16-1 (p < 0,001), expressão do gene Ang-2 e níveis plasmáticos de Bcl-2 (p < 0,001). Quando estratificados por risco, as diferenças foram mantidas com expressão significativamente reduzida em pacientes de alto risco. Foi observada correlação positiva entre miR-15a e plaquetas (R2 = 0,340; p = 0,009), bem como entre Bcl-2 e leucócitos (R2 = 0,310; p = 0,019). Por outro lado, foram observadas correlações negativas entre ZAP-70 e plaquetas (R2 = - 0,334; p = 0,011), entre miR-15a e linfócitos (R2 = - 0,376; p = 0,004), bem como entre miR-16-e linfócitos (R2 = - 0,515; p = 0,00004). Os dados sugerem que uma redução nas expressões de miR-15a e miR-16-1, além de uma superexpressão de Bcl-2, estão associadas à redução da apoptose e, consequentemente, a uma maior sobrevida de linfócitos, contribuindo assim para a acúmulo e agravamento da doença. Por outro lado, a expressão de Ang-2 foi significativamente maior nos grupos A do que nos grupos B + C Binet. Esse contexto leva à especulação de que esse biomarcador deva ser investigado em estudos mais robustos em populações com forma da doença ainda relevantemente indolente, na tentativa de identificar aqueles pacientes com maior potencial de agravamento da doença.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorengUniversidade Federal de Minas GeraisUFMGBrasilFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICASHCL - HOSPITAL DAS CLINICASBrazilian Journal of Pharmaceutical SciencesLeucemia linfocítica crônica de células BRNA MensageiroBiomarcadoresCLLmiR-15amiR-16-1BiomarkersEvaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemiaAvaliação de miR-15a, miR-16-1, ZAP-70, Ang-2 e Bcl-2 como potenciais biomarcadores prognósticos na leucemia linfocítica crônicainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.scielo.br/j/bjps/a/rdTgXzyVgFv7gDcJ56Rxr8r/abstract/?lang=en#Tatiane Vieira BragaFernanda Cristina Gontijo EvangelistaMarie Gabrielle SantiagoAline Lúcia Menezes FerrãoTamara Dauare AlmeidaBarbara Lima da Fonseca BarbosaSérgio Schusterschitz da Silva AraújoGlaciano Nogueira RibeiroMaria das Gracas CarvalhoAdriano de Paula Sabinoapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/61335/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALEvaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia.pdfEvaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia.pdfapplication/pdf549996https://repositorio.ufmg.br/bitstream/1843/61335/2/Evaluation%20of%20miR-15a%2c%20miR-16-1%2c%20ZAP-70%2c%20Ang-2%2c%20and%20Bcl-2%20as%20potential%20prognostic%20biomarkers%20in%20chronic%20lymphocytic%20leukemia.pdfeaa3dad6e3e586dab72e1ed5473b66d6MD521843/613352023-11-23 19:45:05.867oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-11-23T22:45:05Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia |
dc.title.alternative.pt_BR.fl_str_mv |
Avaliação de miR-15a, miR-16-1, ZAP-70, Ang-2 e Bcl-2 como potenciais biomarcadores prognósticos na leucemia linfocítica crônica |
title |
Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia |
spellingShingle |
Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia Tatiane Vieira Braga CLL miR-15a miR-16-1 Biomarkers Leucemia linfocítica crônica de células B RNA Mensageiro Biomarcadores |
title_short |
Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia |
title_full |
Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia |
title_fullStr |
Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia |
title_full_unstemmed |
Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia |
title_sort |
Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia |
author |
Tatiane Vieira Braga |
author_facet |
Tatiane Vieira Braga Fernanda Cristina Gontijo Evangelista Marie Gabrielle Santiago Aline Lúcia Menezes Ferrão Tamara Dauare Almeida Barbara Lima da Fonseca Barbosa Sérgio Schusterschitz da Silva Araújo Glaciano Nogueira Ribeiro Maria das Gracas Carvalho Adriano de Paula Sabino |
author_role |
author |
author2 |
Fernanda Cristina Gontijo Evangelista Marie Gabrielle Santiago Aline Lúcia Menezes Ferrão Tamara Dauare Almeida Barbara Lima da Fonseca Barbosa Sérgio Schusterschitz da Silva Araújo Glaciano Nogueira Ribeiro Maria das Gracas Carvalho Adriano de Paula Sabino |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Tatiane Vieira Braga Fernanda Cristina Gontijo Evangelista Marie Gabrielle Santiago Aline Lúcia Menezes Ferrão Tamara Dauare Almeida Barbara Lima da Fonseca Barbosa Sérgio Schusterschitz da Silva Araújo Glaciano Nogueira Ribeiro Maria das Gracas Carvalho Adriano de Paula Sabino |
dc.subject.por.fl_str_mv |
CLL miR-15a miR-16-1 Biomarkers |
topic |
CLL miR-15a miR-16-1 Biomarkers Leucemia linfocítica crônica de células B RNA Mensageiro Biomarcadores |
dc.subject.other.pt_BR.fl_str_mv |
Leucemia linfocítica crônica de células B RNA Mensageiro Biomarcadores |
description |
Chronic lymphocytic leukemia (CLL) is a blood cancer characterized by the accumulation of clonal B-lymphocytes. This study evaluated the mRNA gene expression of miR-15a, miR-16- 1, ZAP-70, and Ang-2 by qPCR, as well as the plasma levels of Bcl-2 by Elisa immunoassay, in CLL patients and healthy controls. Significant differences were observed when comparing patients and controls regarding miR-15a (p < 0.001), miR-16-1 (p < 0.001) mRNA, Ang-2 gene expression, and Bcl-2 plasma levels (p < 0.001). When stratified by risk, differences were maintained with a significantly reduced expression in high-risk patients. A positive correlation was observed between miR-15a and platelets (R2 = 0.340; p = 0.009) as well as between Bcl-2 and leukocytes (R2 = 0.310; p = 0.019). Conversely, negative correlations were observed between ZAP-70 and platelets (R2 = - 0.334; p = 0.011), between miR-15a and lymphocytes (R2 = - 0.376; p = 0.004), as well as between miR-16-and lymphocytes (R2 = - 0.515; p = 0.00004). The data suggest that a reduction in miR-15a and miR-16-1 expressions, in addition to an overexpression of Bcl-2, are associated with the reduction in apoptosis and, consequently, to a longer survival of lymphocytes, thus contributing to lymphocyte accumulation and aggravation of the disease. By contrast, Ang-2 expression was significantly higher in A than in B + C Binet groups. This context leads to the speculation that this biomarker should be investigated in more robust studies within populations with a still relevantly indolent form of the disease in an attempt to identify those patients with a greater potential for an aggravation of the disease. |
publishDate |
2022 |
dc.date.issued.fl_str_mv |
2022 |
dc.date.accessioned.fl_str_mv |
2023-11-23T22:45:05Z |
dc.date.available.fl_str_mv |
2023-11-23T22:45:05Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/61335 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1590/s2175-97902022e19332 |
dc.identifier.issn.pt_BR.fl_str_mv |
2175-9790 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0002-3944-7235 |
url |
https://doi.org/10.1590/s2175-97902022e19332 http://hdl.handle.net/1843/61335 https://orcid.org/0000-0002-3944-7235 |
identifier_str_mv |
2175-9790 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Brazilian Journal of Pharmaceutical Sciences |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.publisher.initials.fl_str_mv |
UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS HCL - HOSPITAL DAS CLINICAS |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
instname_str |
Universidade Federal de Minas Gerais (UFMG) |
instacron_str |
UFMG |
institution |
UFMG |
reponame_str |
Repositório Institucional da UFMG |
collection |
Repositório Institucional da UFMG |
bitstream.url.fl_str_mv |
https://repositorio.ufmg.br/bitstream/1843/61335/1/License.txt https://repositorio.ufmg.br/bitstream/1843/61335/2/Evaluation%20of%20miR-15a%2c%20miR-16-1%2c%20ZAP-70%2c%20Ang-2%2c%20and%20Bcl-2%20as%20potential%20prognostic%20biomarkers%20in%20chronic%20lymphocytic%20leukemia.pdf |
bitstream.checksum.fl_str_mv |
fa505098d172de0bc8864fc1287ffe22 eaa3dad6e3e586dab72e1ed5473b66d6 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG) |
repository.mail.fl_str_mv |
|
_version_ |
1803589486166147072 |