Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.

The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to net...

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Autores principales:	Patrick N Harter, Jenny Zinke, Alexander Scholz, Julia Tichy, Cornelia Zachskorn, Hans M Kvasnicka, Benjamin Goeppert, Céline Delloye-Bourgeois, Elke Hattingen, Christian Senft, Joachim P Steinbach, Karl H Plate, Patrick Mehlen, Dorothea Schulte, Michel Mittelbronn
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/02239f747ee44b2a98086e30e7b0add9
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spelling	oai:doaj.org-article:02239f747ee44b2a98086e30e7b0add92021-11-18T08:27:17ZNetrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.1932-620310.1371/journal.pone.0092311https://doaj.org/article/02239f747ee44b2a98086e30e7b0add92014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24647424/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to netrin-1 expression. Therefore, the aim of our study was to elucidate the association of netrin-1 expression and patient survival in brain metastases since those constitute one of the most limiting factors for patient prognosis. We investigated 104 brain metastases cases for netrin-1 expression using in-situ hybridization and immunohistochemistry with regard to clinical parameters such as patient survival and MRI data. Our data show that netrin-1 is strongly upregulated in most cancer subtypes. Univariate analyses revealed netrin-1 expression as a significant factor associated with poor patient survival in the total cohort of brain metastasis patients and in sub-entities such as non-small cell lung carcinomas. Interestingly, many cancer samples showed a strong nuclear netrin-1 signal which was recently linked to a truncated netrin-1 variant that enhances tumor growth. Nuclear netrin-1 expression was associated with poor patient survival in univariate as well as in multivariate analyses. Our data indicate both total and nuclear netrin-1 expression as prognostic factors in brain metastases patients in contrast to other prognostic markers in oncology such as patient age, number of brain metastases or Ki67 proliferation index. Therefore, nuclear netrin-1 expression constitutes one of the first reported molecular biomarkers for patient survival in brain metastases. Furthermore, netrin-1 may constitute a promising target for future anti-cancer treatment approaches in brain metastases.Patrick N HarterJenny ZinkeAlexander ScholzJulia TichyCornelia ZachskornHans M KvasnickaBenjamin GoeppertCéline Delloye-BourgeoisElke HattingenChristian SenftJoachim P SteinbachKarl H PlatePatrick MehlenDorothea SchulteMichel MittelbronnPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e92311 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Patrick N Harter Jenny Zinke Alexander Scholz Julia Tichy Cornelia Zachskorn Hans M Kvasnicka Benjamin Goeppert Céline Delloye-Bourgeois Elke Hattingen Christian Senft Joachim P Steinbach Karl H Plate Patrick Mehlen Dorothea Schulte Michel Mittelbronn Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.
description	The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to netrin-1 expression. Therefore, the aim of our study was to elucidate the association of netrin-1 expression and patient survival in brain metastases since those constitute one of the most limiting factors for patient prognosis. We investigated 104 brain metastases cases for netrin-1 expression using in-situ hybridization and immunohistochemistry with regard to clinical parameters such as patient survival and MRI data. Our data show that netrin-1 is strongly upregulated in most cancer subtypes. Univariate analyses revealed netrin-1 expression as a significant factor associated with poor patient survival in the total cohort of brain metastasis patients and in sub-entities such as non-small cell lung carcinomas. Interestingly, many cancer samples showed a strong nuclear netrin-1 signal which was recently linked to a truncated netrin-1 variant that enhances tumor growth. Nuclear netrin-1 expression was associated with poor patient survival in univariate as well as in multivariate analyses. Our data indicate both total and nuclear netrin-1 expression as prognostic factors in brain metastases patients in contrast to other prognostic markers in oncology such as patient age, number of brain metastases or Ki67 proliferation index. Therefore, nuclear netrin-1 expression constitutes one of the first reported molecular biomarkers for patient survival in brain metastases. Furthermore, netrin-1 may constitute a promising target for future anti-cancer treatment approaches in brain metastases.
format	article
author	Patrick N Harter Jenny Zinke Alexander Scholz Julia Tichy Cornelia Zachskorn Hans M Kvasnicka Benjamin Goeppert Céline Delloye-Bourgeois Elke Hattingen Christian Senft Joachim P Steinbach Karl H Plate Patrick Mehlen Dorothea Schulte Michel Mittelbronn
author_facet	Patrick N Harter Jenny Zinke Alexander Scholz Julia Tichy Cornelia Zachskorn Hans M Kvasnicka Benjamin Goeppert Céline Delloye-Bourgeois Elke Hattingen Christian Senft Joachim P Steinbach Karl H Plate Patrick Mehlen Dorothea Schulte Michel Mittelbronn
author_sort	Patrick N Harter
title	Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.
title_short	Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.
title_full	Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.
title_fullStr	Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.
title_full_unstemmed	Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.
title_sort	netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/02239f747ee44b2a98086e30e7b0add9
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Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.

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