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 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.

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Author:Patrick Nikolaus HarterORCiDGND, Jenny Zinke, Alexander Scholz, Julia Frederike Tichy, Cornelia Zachskorn, Hans-Michael KvasnickaORCiD, Benjamin Goeppert, Céline Delloye-Bourgeois, Elke HattingenORCiDGND, Christian Alexander SenftORCiDGND, Joachim Peter SteinbachORCiDGND, Karl H. Plate, Patrick Mehlen, Dorothea Schulte, Michel Guy André Mittelbronn
URN:urn:nbn:de:hebis:30:3-333466
DOI:https://doi.org/10.1371/journal.pone.0092311
ISSN:1932-6203
Parent Title (English):PLoS One
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2014/03/19
Date of first Publication:2014/03/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/03/24
Volume:9
Issue:(3):e92311
Page Number:10
Note:
Copyright: © 2014 Harter et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS-PPN:364360496
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0