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.

Autor:	Pece S; European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy; Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, 20142 Milano, Italy. Electronic address: salvatore.pece@ieo.it., Disalvatore D; European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy., Tosoni D; European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy., Vecchi M; IFOM, The FIRC Institute for Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy., Confalonieri S; European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy., Bertalot G; European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy., Viale G; European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy; Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, 20142 Milano, Italy., Colleoni M; European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy., Veronesi P; European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy; Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, 20142 Milano, Italy., Galimberti V; European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy., Di Fiore PP; European Institute of Oncology IRCCS, Via Ripamonti 435, 20141 Milan, Italy; Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, 20142 Milano, Italy. Electronic address: pierpaolo.difiore@ieo.it.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2019 Apr; Vol. 42, pp. 352-362. Date of Electronic Publication: 2019 Mar 05.
DOI:	10.1016/j.ebiom.2019.02.036
Abstrakt:	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. (Copyright © 2019. Published by Elsevier B.V.)
Databáze:	MEDLINE
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