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Identification and clinical validation of a multigene assay that interrogates the biology of cancer stem cells and predicts metastasis in breast cancer: A retrospective consecutive study

BACKGROUND: Breast cancers show variations in the number and biological aggressiveness of cancer stem cells that correlate with their clinico-prognostic and molecular heterogeneity. Thus, prognostic stratification of breast cancers based on cancer stem cells might help guide patient management. METH...

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Autores principales: Pece, Salvatore, Disalvatore, Davide, Tosoni, Daniela, Vecchi, Manuela, Confalonieri, Stefano, Bertalot, Giovanni, Viale, Giuseppe, Colleoni, Marco, Veronesi, Paolo, Galimberti, Viviana, Di Fiore, Pier Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491379/
https://www.ncbi.nlm.nih.gov/pubmed/30846393
http://dx.doi.org/10.1016/j.ebiom.2019.02.036
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author Pece, Salvatore
Disalvatore, Davide
Tosoni, Daniela
Vecchi, Manuela
Confalonieri, Stefano
Bertalot, Giovanni
Viale, Giuseppe
Colleoni, Marco
Veronesi, Paolo
Galimberti, Viviana
Di Fiore, Pier Paolo
author_facet Pece, Salvatore
Disalvatore, Davide
Tosoni, Daniela
Vecchi, Manuela
Confalonieri, Stefano
Bertalot, Giovanni
Viale, Giuseppe
Colleoni, Marco
Veronesi, Paolo
Galimberti, Viviana
Di Fiore, Pier Paolo
author_sort Pece, Salvatore
collection PubMed
description BACKGROUND: Breast cancers show variations in the number and biological aggressiveness of cancer stem cells that correlate with their clinico-prognostic and molecular heterogeneity. Thus, prognostic stratification of breast cancers based on cancer stem cells might help guide patient management. METHODS: We derived a 20-gene stem cell signature from the transcriptional profile of normal mammary stem cells, capable of identifying breast cancers with a homogeneous profile and poor prognosis in in silico analyses. The clinical value of this signature was assessed in a prospective-retrospective cohort of 2, 453 breast cancer patients. Models for predicting individual risk of metastasis were developed from expression data of the 20 genes in patients randomly assigned to a training set, using the ridge-penalized Cox regression, and tested in an independent validation set. FINDINGS: Analyses revealed that the 20-gene stem cell signature provided prognostic information in Triple-Negative and Luminal breast cancer patients, independently of standard clinicopathological parameters. Through functional studies in individual tumours, we correlated the risk score assigned by the signature with the proliferative and self-renewal potential of the cancer stem cell population. By retraining the 20-gene signature in Luminal patients, we derived the risk model, StemPrintER, which predicted early and late recurrence independently of standard prognostic factors. INTERPRETATION: Our findings indicate that the 20-gene stem cell signature, by its unique ability to interrogate the biology of cancer stem cells of the primary tumour, provides a reliable estimate of metastatic risk in Triple-Negative and Luminal breast cancer patients independently of standard clinicopathological parameters.
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spelling pubmed-64913792019-05-06 Identification and clinical validation of a multigene assay that interrogates the biology of cancer stem cells and predicts metastasis in breast cancer: A retrospective consecutive study Pece, Salvatore Disalvatore, Davide Tosoni, Daniela Vecchi, Manuela Confalonieri, Stefano Bertalot, Giovanni Viale, Giuseppe Colleoni, Marco Veronesi, Paolo Galimberti, Viviana Di Fiore, Pier Paolo EBioMedicine Research paper BACKGROUND: Breast cancers show variations in the number and biological aggressiveness of cancer stem cells that correlate with their clinico-prognostic and molecular heterogeneity. Thus, prognostic stratification of breast cancers based on cancer stem cells might help guide patient management. METHODS: We derived a 20-gene stem cell signature from the transcriptional profile of normal mammary stem cells, capable of identifying breast cancers with a homogeneous profile and poor prognosis in in silico analyses. The clinical value of this signature was assessed in a prospective-retrospective cohort of 2, 453 breast cancer patients. Models for predicting individual risk of metastasis were developed from expression data of the 20 genes in patients randomly assigned to a training set, using the ridge-penalized Cox regression, and tested in an independent validation set. FINDINGS: Analyses revealed that the 20-gene stem cell signature provided prognostic information in Triple-Negative and Luminal breast cancer patients, independently of standard clinicopathological parameters. Through functional studies in individual tumours, we correlated the risk score assigned by the signature with the proliferative and self-renewal potential of the cancer stem cell population. By retraining the 20-gene signature in Luminal patients, we derived the risk model, StemPrintER, which predicted early and late recurrence independently of standard prognostic factors. INTERPRETATION: Our findings indicate that the 20-gene stem cell signature, by its unique ability to interrogate the biology of cancer stem cells of the primary tumour, provides a reliable estimate of metastatic risk in Triple-Negative and Luminal breast cancer patients independently of standard clinicopathological parameters. Elsevier 2019-03-05 /pmc/articles/PMC6491379/ /pubmed/30846393 http://dx.doi.org/10.1016/j.ebiom.2019.02.036 Text en © 2019 The Authors. Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Pece, Salvatore
Disalvatore, Davide
Tosoni, Daniela
Vecchi, Manuela
Confalonieri, Stefano
Bertalot, Giovanni
Viale, Giuseppe
Colleoni, Marco
Veronesi, Paolo
Galimberti, Viviana
Di Fiore, Pier Paolo
Identification and clinical validation of a multigene assay that interrogates the biology of cancer stem cells and predicts metastasis in breast cancer: A retrospective consecutive study
title Identification and clinical validation of a multigene assay that interrogates the biology of cancer stem cells and predicts metastasis in breast cancer: A retrospective consecutive study
title_full Identification and clinical validation of a multigene assay that interrogates the biology of cancer stem cells and predicts metastasis in breast cancer: A retrospective consecutive study
title_fullStr Identification and clinical validation of a multigene assay that interrogates the biology of cancer stem cells and predicts metastasis in breast cancer: A retrospective consecutive study
title_full_unstemmed Identification and clinical validation of a multigene assay that interrogates the biology of cancer stem cells and predicts metastasis in breast cancer: A retrospective consecutive study
title_short Identification and clinical validation of a multigene assay that interrogates the biology of cancer stem cells and predicts metastasis in breast cancer: A retrospective consecutive study
title_sort identification and clinical validation of a multigene assay that interrogates the biology of cancer stem cells and predicts metastasis in breast cancer: a retrospective consecutive study
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491379/
https://www.ncbi.nlm.nih.gov/pubmed/30846393
http://dx.doi.org/10.1016/j.ebiom.2019.02.036
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