Germline genetic variants of the renin-angiotensin system, hypoxia and angiogenesis in non-small cell lung cancer progression : discovery and validation studies
| Autor(a) principal: | |
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| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , , , , |
| 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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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:RCAAP2023-07-14T15:34:30ZPortal AgregadorONG |
| 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 |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/47160 |
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http://hdl.handle.net/10451/47160 |
| dc.language.iso.fl_str_mv |
eng |
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eng |
| dc.relation.none.fl_str_mv |
Cancers 12, no. 12: 3834 10.3390/cancers12123834 2072-6694 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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MDPI |
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MDPI |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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