HERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcome
Autor(a) principal: | |
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Data de Publicação: | 2021 |
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/10451/46534 |
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/. |
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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 |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Springer Nature |
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Springer Nature |
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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) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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