HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome

Detalhes bibliográficos
Autor(a) principal: Golkaram, Mahdi
Data de Publicação: 2021
Outros Autores: Salmans, Michael L., Kaplan, Shannon, Vijayaraghavan, Raakhee, Martins, Marta, Khan, Nafeesa, Garbutt, Cassandra, Wise, Aaron, Yao, Joyee, Casimiro, Sandra, Marques, Catarina, Macedo, Daniela, Costa, Ana Lúcia, Alvim, Cecilia, Mansinho, André, Filipe, Pedro, Marques da Costa, Pedro, Fernandes, Afonso, Borralho, Paula, Ferreira, Cristina, Aldeia, Fernando, Malaquias, João, Godsey, Jim, So, Alex, Pawlowski, Traci, Costa, Luis, Zhang, Shile, Liu, Li
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/46534
Resumo: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
id RCAP_df2509bfabcde8c63a457d9ddc7ee5aa
oai_identifier_str oai:repositorio.ul.pt:10451/46534
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Colorectal cancer (CRC) is one of the most lethal malignancies. The extreme heterogeneity in survival rate is driving the need for new prognostic biomarkers. Human endogenous retroviruses (hERVs) have been suggested to influence tumor progression, oncogenesis and elicit an immune response. We examined multiple next-generation sequencing (NGS)-derived biomarkers in 114 CRC patients with paired whole-exome and whole-transcriptome sequencing (WES and WTS, respectively). First, we demonstrate that the median expression of hERVs can serve as a potential biomarker for prognosis, relapse, and resistance to chemotherapy in stage II and III CRC. We show that hERV expression and CD8+ tumor-infiltrating T-lymphocytes (TILs) synergistically stratify overall and relapse-free survival (OS and RFS): the median OS of the CD8-/hERV+ subgroup was 29.8 months compared with 37.5 months for other subgroups (HR = 4.4, log-rank P < 0.001). Combing NGS-based biomarkers (hERV/CD8 status) with clinicopathological factors provided a better prediction of patient survival compared to clinicopathological factors alone. Moreover, we explored the association between genomic and transcriptomic features of tumors with high hERV expression and establish this subtype as distinct from previously described consensus molecular subtypes of CRC. Overall, our results underscore a previously unknown role for hERVs in leading to a more aggressive subtype of CRC.The biobanking of CRC from Hospital Santa Maria, Lisbon, Portugal, was supported by a grant from the Official Portuguese Funding Agency for Science and Technology (FCT: PIC/IC/82821/2007).Springer NatureRepositório da Universidade de LisboaGolkaram, MahdiSalmans, Michael L.Kaplan, ShannonVijayaraghavan, RaakheeMartins, MartaKhan, NafeesaGarbutt, CassandraWise, AaronYao, JoyeeCasimiro, SandraMarques, CatarinaMacedo, DanielaCosta, Ana LúciaAlvim, CeciliaMansinho, AndréFilipe, PedroMarques da Costa, PedroFernandes, AfonsoBorralho, PaulaFerreira, CristinaAldeia, FernandoMalaquias, JoãoGodsey, JimSo, AlexPawlowski, TraciCosta, LuisZhang, ShileLiu, Li2021-02-25T18:20:29Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/46534engNPJ Genom Med. 2021 Feb 15;6(1):1310.1038/s41525-021-00177-w2056-7944info: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:RCAAP2023-11-08T16:48:53Zoai:repositorio.ul.pt:10451/46534Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:58:42.049843Repositório 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 HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome
title HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome
spellingShingle HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome
Golkaram, Mahdi
title_short HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome
title_full HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome
title_fullStr HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome
title_full_unstemmed HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome
title_sort HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome
author Golkaram, Mahdi
author_facet Golkaram, Mahdi
Salmans, Michael L.
Kaplan, Shannon
Vijayaraghavan, Raakhee
Martins, Marta
Khan, Nafeesa
Garbutt, Cassandra
Wise, Aaron
Yao, Joyee
Casimiro, Sandra
Marques, Catarina
Macedo, Daniela
Costa, Ana Lúcia
Alvim, Cecilia
Mansinho, André
Filipe, Pedro
Marques da Costa, Pedro
Fernandes, Afonso
Borralho, Paula
Ferreira, Cristina
Aldeia, Fernando
Malaquias, João
Godsey, Jim
So, Alex
Pawlowski, Traci
Costa, Luis
Zhang, Shile
Liu, Li
author_role author
author2 Salmans, Michael L.
Kaplan, Shannon
Vijayaraghavan, Raakhee
Martins, Marta
Khan, Nafeesa
Garbutt, Cassandra
Wise, Aaron
Yao, Joyee
Casimiro, Sandra
Marques, Catarina
Macedo, Daniela
Costa, Ana Lúcia
Alvim, Cecilia
Mansinho, André
Filipe, Pedro
Marques da Costa, Pedro
Fernandes, Afonso
Borralho, Paula
Ferreira, Cristina
Aldeia, Fernando
Malaquias, João
Godsey, Jim
So, Alex
Pawlowski, Traci
Costa, Luis
Zhang, Shile
Liu, Li
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
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 Golkaram, Mahdi
Salmans, Michael L.
Kaplan, Shannon
Vijayaraghavan, Raakhee
Martins, Marta
Khan, Nafeesa
Garbutt, Cassandra
Wise, Aaron
Yao, Joyee
Casimiro, Sandra
Marques, Catarina
Macedo, Daniela
Costa, Ana Lúcia
Alvim, Cecilia
Mansinho, André
Filipe, Pedro
Marques da Costa, Pedro
Fernandes, Afonso
Borralho, Paula
Ferreira, Cristina
Aldeia, Fernando
Malaquias, João
Godsey, Jim
So, Alex
Pawlowski, Traci
Costa, Luis
Zhang, Shile
Liu, Li
description © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
publishDate 2021
dc.date.none.fl_str_mv 2021-02-25T18:20:29Z
2021
2021-01-01T00:00:00Z
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/10451/46534
url http://hdl.handle.net/10451/46534
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv NPJ Genom Med. 2021 Feb 15;6(1):13
10.1038/s41525-021-00177-w
2056-7944
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 Springer Nature
publisher.none.fl_str_mv Springer Nature
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
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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
repository.mail.fl_str_mv
_version_ 1799134533264605184