Open Access Open Badges Research article

Serum biomarkers for neurofibromatosis type 1 and early detection of malignant peripheral nerve-sheath tumors

Su-Jin Park1, Birgit Sawitzki2, Lan Kluwe3, Victor F Mautner3, Nikola Holtkamp1 and Andreas Kurtz14*

Author affiliations

1 Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany

2 Institute for Clinical Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany

3 Experimental Tumor Research, Phakomatoses, Department of Neurology, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany

4 College of Veterinary Medicine, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, Republic Korea

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Citation and License

BMC Medicine 2013, 11:109  doi:10.1186/1741-7015-11-109

Published: 23 April 2013



Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome characterized by the development of benign nerve-sheath tumors, which transform to malignant peripheral nerve-sheath tumors (MPNST) in about 8 to 13% of patients with NF1. MPNST are invasive sarcomas with extremely poor prognosis, and their development may correlate with internal tumor load of patients with NF1. Because early identification of patients with NF1 at risk for developing MPNST should improve their clinical outcome, the aim of this study was to identify serum biomarkers for tumor progression in NF1, and to analyze their correlation with tumor type and internal tumor load.


We selected candidate biomarkers for NF1 by manually mining published data sources, and conducted a systematic screen of 56 candidate serum biomarkers using customized antibody arrays. Serum from 104 patients with NF1 with and without MPNST, and from 41 healthy control subjects, was analyzed. Statistical analysis was performed using the non-parametric Mann–Whitney U-test, followed by Bonferroni correction.


Our analysis identified four markers (epidermal growth factor receptor, interferon-γ, interleukin-6, and tumor necrosis factor-α) for which significantly different serum concentrations were seen in patients with NF1 compared with healthy controls. Two markers (insulin-like growth factor binding protein 1 (IGFBP1) and regulated upon activation, normal T-cell expressed and secreted (RANTES)) showed significantly higher concentrations in patients with NF1 and MPNST compared with patients with NF1 without MPNST. A correlation with internal tumor load was found for IGFBP1.


Our study identified two serum markers with potential for early detection of patients with NF1 at risk for developing MPNST, and four markers that could distinguish between patients with NF1 and healthy subjects. Such markers may be useful as diagnostic tools to support the diagnosis of NF1 and for timely identification of MPNST. Moreover, the data suggest that there is a systemic increase in inflammatory cytokines independently of tumor load in patients with NF1.

Neurofibromatosis type 1; Serum biomarker; Antibody array; Cytokines; Malignant peripheral nerve-sheath tumor