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

2021Artigo científico Acesso aberto
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dc.contributor.authorGolkaram, Mahdi
dc.contributor.authorSalmans, Michael L.
dc.contributor.authorKaplan, Shannon
dc.contributor.authorVijayaraghavan, Raakhee
dc.contributor.authorMartins, Marta
dc.contributor.authorKhan, Nafeesa
dc.contributor.authorGarbutt, Cassandra
dc.contributor.authorWise, Aaron
dc.contributor.authorYao, Joyee
dc.contributor.authorCasimiro, Sandra
dc.contributor.authorMarques, Catarina
dc.contributor.authorMacedo, Daniela
dc.contributor.authorCosta, Ana Lúcia
dc.contributor.authorAlvim, Cecilia
dc.contributor.authorMansinho, André
dc.contributor.authorFilipe, Pedro
dc.contributor.authorMarques da Costa, Pedro
dc.contributor.authorFernandes, Afonso
dc.contributor.authorBorralho, Paula
dc.contributor.authorFerreira, Cristina
dc.contributor.authorAldeia, Fernando
dc.contributor.authorMalaquias, João
dc.contributor.authorGodsey, Jim
dc.contributor.authorSo, Alex
dc.contributor.authorPawlowski, Traci
dc.contributor.authorCosta, Luis
dc.contributor.authorZhang, Shile
dc.contributor.authorLiu, Li
dc.date.accessioned2021-02-25T18:20:29Z
dc.date.available2021-02-25T18:20:29Z
dc.date.issued2021
dc.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/.pt_PT
dc.description.abstractColorectal 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.pt_PT
dc.description.sponsorshipThe 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).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNPJ Genom Med. 2021 Feb 15;6(1):13pt_PT
dc.identifier.doi10.1038/s41525-021-00177-wpt_PT
dc.identifier.eissn2056-7944
dc.identifier.urihttp://hdl.handle.net/10451/46534
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relation.publisherversionhttps://www.nature.com/npjgenmedpt_PT
dc.titleHERVs establish a distinct molecular subtype in stage II/III colorectal cancer with poor outcomept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5646-ICCMS/PIC%2FIC%2F82821%2F2007/PT
oaire.citation.issue1pt_PT
oaire.citation.startPage13pt_PT
oaire.citation.titleNPJ Genomic Medicinept_PT
oaire.citation.volume6pt_PT
oaire.fundingStream5646-ICCMS
person.familyNameMartins
person.familyNameCara de Anjo Casimiro
person.familyNameMarques
person.familyNameMelo Alvim
person.familyNameMansinho
person.familyNameMarques da Costa
person.familyNameBorralho Nunes
person.familyNameCosta
person.givenNameMarta
person.givenNameSandra Cristina
person.givenNameCatarina
person.givenNameCecilia
person.givenNameAndré
person.givenNamePedro
person.givenNamePaula
person.givenNameLuis
person.identifier.ciencia-id0F12-5181-0B22
person.identifier.ciencia-idB311-6AE6-9A83
person.identifier.ciencia-idEC14-06B2-7253
person.identifier.ciencia-id7614-C999-F6C7
person.identifier.ciencia-idE91A-B8A4-D3B9
person.identifier.ciencia-id041E-4ADE-FB64
person.identifier.orcid0000-0003-0429-9380
person.identifier.orcid0000-0002-6917-4477
person.identifier.orcid0000-0003-3558-3966
person.identifier.orcid0000-0001-8771-0838
person.identifier.orcid0000-0002-6123-8288
person.identifier.orcid0000-0002-8556-2090
person.identifier.orcid0000-0002-4782-7318
person.identifier.scopus-author-id55268246400
person.identifier.scopus-author-id14043403400
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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