Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning

Abstract The identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead...

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Autores principales:	Kalifa Manjang, Shailesh Tripathi, Olli Yli-Harja, Matthias Dehmer, Galina Glazko, Frank Emmert-Streib
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/05e4f37fd1ac4cefba70c6651c466311
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spelling	oai:doaj.org-article:05e4f37fd1ac4cefba70c6651c4663112021-12-02T11:46:06ZPrognostic gene expression signatures of breast cancer are lacking a sensible biological meaning10.1038/s41598-020-79375-y2045-2322https://doaj.org/article/05e4f37fd1ac4cefba70c6651c4663112021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79375-yhttps://doaj.org/toc/2045-2322Abstract The identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead to novel insights of disease mechanisms and the underlying molecular processes that cause the pathological behavior. For breast cancer, many signatures based on gene expression values have been reported to be associated with overall survival. Consequently, such signatures have been used for suggesting biological explanations of breast cancer and drug mechanisms. In this paper, we demonstrate for a large number of breast cancer signatures that such an implication is not justified. Our approach eliminates systematically all traces of biological meaning of signature genes and shows that among the remaining genes, surrogate gene sets can be formed with indistinguishable prognostic prediction capabilities and opposite biological meaning. Hence, our results demonstrate that none of the studied signatures has a sensible biological interpretation or meaning with respect to disease etiology. Overall, this shows that prognostic signatures are black-box models with sensible predictions of breast cancer outcome but no value for revealing causal connections. Furthermore, we show that the number of such surrogate gene sets is not small but very large.Kalifa ManjangShailesh TripathiOlli Yli-HarjaMatthias DehmerGalina GlazkoFrank Emmert-StreibNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kalifa Manjang Shailesh Tripathi Olli Yli-Harja Matthias Dehmer Galina Glazko Frank Emmert-Streib Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning
description	Abstract The identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead to novel insights of disease mechanisms and the underlying molecular processes that cause the pathological behavior. For breast cancer, many signatures based on gene expression values have been reported to be associated with overall survival. Consequently, such signatures have been used for suggesting biological explanations of breast cancer and drug mechanisms. In this paper, we demonstrate for a large number of breast cancer signatures that such an implication is not justified. Our approach eliminates systematically all traces of biological meaning of signature genes and shows that among the remaining genes, surrogate gene sets can be formed with indistinguishable prognostic prediction capabilities and opposite biological meaning. Hence, our results demonstrate that none of the studied signatures has a sensible biological interpretation or meaning with respect to disease etiology. Overall, this shows that prognostic signatures are black-box models with sensible predictions of breast cancer outcome but no value for revealing causal connections. Furthermore, we show that the number of such surrogate gene sets is not small but very large.
format	article
author	Kalifa Manjang Shailesh Tripathi Olli Yli-Harja Matthias Dehmer Galina Glazko Frank Emmert-Streib
author_facet	Kalifa Manjang Shailesh Tripathi Olli Yli-Harja Matthias Dehmer Galina Glazko Frank Emmert-Streib
author_sort	Kalifa Manjang
title	Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning
title_short	Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning
title_full	Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning
title_fullStr	Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning
title_full_unstemmed	Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning
title_sort	prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/05e4f37fd1ac4cefba70c6651c466311
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Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning

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