Germline genetic variants of the renin-angiotensin system, hypoxia and angiogenesis in non-small cell lung cancer progression : discovery and validation studies

Detalhes bibliográficos
Autor(a) principal: Catarata, Maria Joana
Data de Publicação: 2020
Outros Autores: Medeiros, Rui, Oliveira, Maria José, Pêgo, Alice, Frade, João Gonçalo, Martins, Maria Fátima, Robalo Cordeiro, Carlos Robalo, Herth, Felix J F, Thomas, Michael, Kriegsmann, Mark, Meister, Michael, Schneider, Marc A, Muley, Thomas, Ribeiro, Ricardo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/47160
Resumo: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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spelling Germline genetic variants of the renin-angiotensin system, hypoxia and angiogenesis in non-small cell lung cancer progression : discovery and validation studiesGenetic polymorphismsLung cancerRenin–angiotensinHypoxiaAngiogenesis© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Introduction: The renin–angiotensin system (RAS) is involved in cell proliferation, immunoinflammatory response, hypoxia and angiogenesis, which are critical biological processes in lung cancer. Our aim was to study the association of putatively functional genetic polymorphisms in genes coding for proteins involved in RAS, hypoxia and angiogenesis with non-small cell lung cancer (NSCLC) prognosis. Methods: Genotyping of 52 germline variants from genes of the RAS and hypoxic/angiogenic factors/receptors was performed using MassARRAY iPLEX Gold in a retrospective cohort (n = 167) of advanced NSCLC patients. Validation of the resulting genetic markers was conducted in an independent group (n = 190), matched by clinicopathological characteristics. Results: Multivariate analysis on the discovery set revealed that MME rs701109 C carriers were protected from disease progression in comparison with homozygous T (hazard ratio (HR) = 0.5, 95% confidence interval (CI) = 0.2–0.8, p = 0.010). Homozygous A and T genotypes for KDR rs1870377 were at increased risk for disease progression and death compared to heterozygous (HR = 1.7, 95% CI = 1.2–2.5, p = 0.005 and HR = 2.1, 95% CI = 1.2–3.4, p = 0.006, respectively). Carriers of homozygous genotypes for ACE2 rs908004 presented increased risk for disease progression, only in the subgroup of patients without tumour actionable driver mutations (HR = 2.9, 95% CI = 1.3–6.3, p = 0.010). Importantly, the association of homozygous genotypes in MME rs701109 with risk for disease progression was confirmed after multivariate analysis in the validation set. Conclusion: This study provides evidence that MME polymorphism, which encodes neprilysin, may modulate progression-free survival in advanced NSCLC. Present genetic variation findings will foster basic, translational, and clinical research on their role in NSCLC.M.J.C. was supported by the Associação de Estudos Respiratórios and the Portuguese Pulmonology Society.MDPIRepositório da Universidade de LisboaCatarata, Maria JoanaMedeiros, RuiOliveira, Maria JoséPêgo, AliceFrade, João GonçaloMartins, Maria FátimaRobalo Cordeiro, Carlos RobaloHerth, Felix J FThomas, MichaelKriegsmann, MarkMeister, MichaelSchneider, Marc AMuley, ThomasRibeiro, Ricardo2021-03-30T15:28:54Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/47160engCancers 12, no. 12: 383410.3390/cancers121238342072-6694info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:49:51Zoai:repositorio.ul.pt:10451/47160Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:59:14.139069Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Germline genetic variants of the renin-angiotensin system, hypoxia and angiogenesis in non-small cell lung cancer progression : discovery and validation studies
title Germline genetic variants of the renin-angiotensin system, hypoxia and angiogenesis in non-small cell lung cancer progression : discovery and validation studies
spellingShingle Germline genetic variants of the renin-angiotensin system, hypoxia and angiogenesis in non-small cell lung cancer progression : discovery and validation studies
Catarata, Maria Joana
Genetic polymorphisms
Lung cancer
Renin–angiotensin
Hypoxia
Angiogenesis
title_short Germline genetic variants of the renin-angiotensin system, hypoxia and angiogenesis in non-small cell lung cancer progression : discovery and validation studies
title_full Germline genetic variants of the renin-angiotensin system, hypoxia and angiogenesis in non-small cell lung cancer progression : discovery and validation studies
title_fullStr Germline genetic variants of the renin-angiotensin system, hypoxia and angiogenesis in non-small cell lung cancer progression : discovery and validation studies
title_full_unstemmed Germline genetic variants of the renin-angiotensin system, hypoxia and angiogenesis in non-small cell lung cancer progression : discovery and validation studies
title_sort Germline genetic variants of the renin-angiotensin system, hypoxia and angiogenesis in non-small cell lung cancer progression : discovery and validation studies
author Catarata, Maria Joana
author_facet Catarata, Maria Joana
Medeiros, Rui
Oliveira, Maria José
Pêgo, Alice
Frade, João Gonçalo
Martins, Maria Fátima
Robalo Cordeiro, Carlos Robalo
Herth, Felix J F
Thomas, Michael
Kriegsmann, Mark
Meister, Michael
Schneider, Marc A
Muley, Thomas
Ribeiro, Ricardo
author_role author
author2 Medeiros, Rui
Oliveira, Maria José
Pêgo, Alice
Frade, João Gonçalo
Martins, Maria Fátima
Robalo Cordeiro, Carlos Robalo
Herth, Felix J F
Thomas, Michael
Kriegsmann, Mark
Meister, Michael
Schneider, Marc A
Muley, Thomas
Ribeiro, Ricardo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Catarata, Maria Joana
Medeiros, Rui
Oliveira, Maria José
Pêgo, Alice
Frade, João Gonçalo
Martins, Maria Fátima
Robalo Cordeiro, Carlos Robalo
Herth, Felix J F
Thomas, Michael
Kriegsmann, Mark
Meister, Michael
Schneider, Marc A
Muley, Thomas
Ribeiro, Ricardo
dc.subject.por.fl_str_mv Genetic polymorphisms
Lung cancer
Renin–angiotensin
Hypoxia
Angiogenesis
topic Genetic polymorphisms
Lung cancer
Renin–angiotensin
Hypoxia
Angiogenesis
description © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-01-01T00:00:00Z
2021-03-30T15:28:54Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/47160
url http://hdl.handle.net/10451/47160
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Cancers 12, no. 12: 3834
10.3390/cancers12123834
2072-6694
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 MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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