Prognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors

Abstract Centrosome amplification (CA) is a hallmark of cancer, observable in ≥75% of breast tumors. CA drives aggressive cellular phenotypes such as chromosomal instability (CIN) and invasiveness. Thus, assessment of CA may offer insights into the prognosis of breast cancer and identify patients wh...

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Autores principales:	Angela Ogden, Padmashree C. G. Rida, Ritu Aneja
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af3e01983a1a4d65aef64bb6f7c66452
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spelling	oai:doaj.org-article:af3e01983a1a4d65aef64bb6f7c664522021-12-02T11:41:22ZPrognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors10.1038/s41598-017-00363-w2045-2322https://doaj.org/article/af3e01983a1a4d65aef64bb6f7c664522017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00363-whttps://doaj.org/toc/2045-2322Abstract Centrosome amplification (CA) is a hallmark of cancer, observable in ≥75% of breast tumors. CA drives aggressive cellular phenotypes such as chromosomal instability (CIN) and invasiveness. Thus, assessment of CA may offer insights into the prognosis of breast cancer and identify patients who might benefit from centrosome declustering agents. However, it remains unclear whether CA is correlated with clinical outcomes after adjusting for confounding factors. To gain insights, we developed a signature, “CA20”, comprising centrosome structural genes and genes whose dysregulation is implicated in inducing CA. We found that CA20 was a significant independent predictor of worse survival in two large independent datasets after adjusting for potentially confounding factors. In multivariable analyses including both CA20 and CIN25 (a gene expression-based score that correlates with aneuploidy and has prognostic value in many types of cancer), only CA20 was significant, suggesting CA20 captures the risk-predictive information of CIN25 and offers information beyond it. CA20 correlated strongly with CIN25, so a high CA20 score may reflect tumors with high CIN and potentially other aggressive features that may require more aggressive treatment. Finally, we identified processes and pathways differing between CA20-low and high groups that may be valuable therapeutic targets.Angela OgdenPadmashree C. G. RidaRitu AnejaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angela Ogden Padmashree C. G. Rida Ritu Aneja Prognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors
description	Abstract Centrosome amplification (CA) is a hallmark of cancer, observable in ≥75% of breast tumors. CA drives aggressive cellular phenotypes such as chromosomal instability (CIN) and invasiveness. Thus, assessment of CA may offer insights into the prognosis of breast cancer and identify patients who might benefit from centrosome declustering agents. However, it remains unclear whether CA is correlated with clinical outcomes after adjusting for confounding factors. To gain insights, we developed a signature, “CA20”, comprising centrosome structural genes and genes whose dysregulation is implicated in inducing CA. We found that CA20 was a significant independent predictor of worse survival in two large independent datasets after adjusting for potentially confounding factors. In multivariable analyses including both CA20 and CIN25 (a gene expression-based score that correlates with aneuploidy and has prognostic value in many types of cancer), only CA20 was significant, suggesting CA20 captures the risk-predictive information of CIN25 and offers information beyond it. CA20 correlated strongly with CIN25, so a high CA20 score may reflect tumors with high CIN and potentially other aggressive features that may require more aggressive treatment. Finally, we identified processes and pathways differing between CA20-low and high groups that may be valuable therapeutic targets.
format	article
author	Angela Ogden Padmashree C. G. Rida Ritu Aneja
author_facet	Angela Ogden Padmashree C. G. Rida Ritu Aneja
author_sort	Angela Ogden
title	Prognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors
title_short	Prognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors
title_full	Prognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors
title_fullStr	Prognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors
title_full_unstemmed	Prognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors
title_sort	prognostic value of ca20, a score based on centrosome amplification-associated genes, in breast tumors
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/af3e01983a1a4d65aef64bb6f7c66452
work_keys_str_mv	AT angelaogden prognosticvalueofca20ascorebasedoncentrosomeamplificationassociatedgenesinbreasttumors AT padmashreecgrida prognosticvalueofca20ascorebasedoncentrosomeamplificationassociatedgenesinbreasttumors AT rituaneja prognosticvalueofca20ascorebasedoncentrosomeamplificationassociatedgenesinbreasttumors
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Prognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors

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