The prognostic potential of alternative transcript isoforms across human tumors
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- dc.contributor.author Trincado Alonso, Juan Luis, 1987-ca
- dc.contributor.author Sebestyén, Endreca
- dc.contributor.author Pagès Pinós, Amadísca
- dc.contributor.author Eyras Jiménez, Eduardoca
- dc.date.accessioned 2016-11-16T12:35:34Z
- dc.date.available 2016-11-16T12:35:34Z
- dc.date.issued 2016ca
- dc.description.abstract Background: Phenotypic changes during cancer progression are associated with alterations in gene expression, which can be exploited to build molecular signatures for tumor stage identification and prognosis. However, it is not yet known whether the relative abundance of transcript isoforms may be informative for clinical stage and survival. Methods: Using information theory and machine learning methods, we integrated RNA sequencing and clinical data from The Cancer Genome Atlas project to perform the first systematic analysis of the prognostic potential of transcript isoforms in 12 solid tumors to build new signatures for stage and prognosis. This study was also performed in breast tumors according to estrogen receptor (ER) status and melanoma tumors with proliferative and invasive phenotypes. Results: Transcript isoform signatures accurately separate early from late-stage groups and metastatic from non-metastatic tumors, and are predictive of the survival of patients with undetermined lymph node invasion or metastatic status. These signatures show similar, and sometimes better, accuracies compared with known gene expression signatures in retrospective data and are largely independent of gene expression changes. Furthermore, we show frequent transcript isoform changes in breast tumors according to ER status, and in melanoma tumors according to the invasive or proliferative phenotype, and derive accurate predictive models of stage and survival within each patient subgroup. Conclusions: Our analyses reveal new signatures based on transcript isoform abundances that characterize tumor phenotypes and their progression independently of gene expression. Transcript isoform signatures appear especially relevant to determine lymph node invasion and metastasis and may potentially contribute towards current strategies of precision cancer medicine.
- dc.description.sponsorship This work was supported by grants BIO2014-52566-R and Consolider RNAREG (CSD2009-00080) from the MINECO (Spanish Government) and FEDER, by AGAUR (2014-SGR1121) and by the Sandra Ibarra Foundation for Cancer (FSI2013).
- dc.format.mimetype application/pdfca
- dc.identifier.citation Trincado Alonso J, Sebestyén E, Pagés A, Eyras E. The prognostic potential of alternative transcript isoforms across human tumors. Genome Medicine. 2016;8(1):85. DOI: 10.1186/s13073-016-0339-3ca
- dc.identifier.doi http://dx.doi.org/10.1186/s13073-016-0339-3
- dc.identifier.issn 1756-994Xca
- dc.identifier.uri http://hdl.handle.net/10230/27525
- dc.language.iso engca
- dc.publisher BioMed Centralca
- dc.relation.ispartof Genome Medicine. 2016;8(1):85
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2014-52566-R
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00080
- dc.rights © 2016 The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Tumors
- dc.title The prognostic potential of alternative transcript isoforms across human tumorsca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca