Netrin-1 Expression Is an Independent Prognostic Factor for Poor Patient Survival in Brain Metastases
Open accessAbstract
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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Neoplastic cells often escape dependence receptor-mediated RCD by upregulating expression of cognate ligands such as NTN1.
“(1) upregulating the expression of their cognate ligands such as NTN1 [360–362]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [362]
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Self-citation
- Authors
- Harter, P. N., Zinke, J., Scholz, A., Tichy, J., Zachskorn, C., Kvasnicka, H. M., Goeppert, B., Delloye-Bourgeois, C., Hattingen, E., Senft, C., Steinbach, J. P., Plate, K. H., Mehlen, P., Schulte, D., & Mittelbronn, M.
- Affiliations
- Goethe University Frankfurt (DE)
- German Cancer Research Center (DE)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Mittelbronn, Michel
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-03-19
- Volume
- 9
- Issue
- 3
- Pages
- e92311
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3960244
- OpenAlex
- W1984599104
- Cited by
- 41
- References
- 39
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 1 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 3
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
- Funders
- Goethe-Universität Frankfurt am Main
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Brain Metastases and Treatment
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- netrin-1, brain metastases, prognostic factors, patient survival, non-small cell lung cancer, tumor progression, molecular biomarkers, cancer therapy targets
- MeSH terms
- Netrin-1, Brain Neoplasms, Humans, Immunohistochemistry, Nerve Growth Factors, Prognosis, In Situ Hybridization, Ki-67 Antigen, Tumor Suppressor Proteins
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