Figure 1

Schematic outline of the candidate marker selection and screening procedures. The initial 115 possible serum markers for neurofibromatosis type 1 (NF1) tumors consisted of proteins that are overexpressed in plexiform neurofibromas (PNF) or malignant peripheral nerve-sheath tumors (MPNST), have been found to promote tumor growth (n = 79), or are immunmodulatory cytokines (n = 36). These 115 proteins were selected by manual searches of published data. Of the 115 initially selected proteins, 56 were screened in two steps, with sera from 60 patients with NF1 in the first pre-screening step, and from 104 patients with NF1 in the second. Five proteins (platelet-derived growth factor (PDGF)-BB, insulin-like growth factor binding protein (IGFBP)1, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-4 and TNF-related apoptosis inducing ligand (TRAIL)-R2) were selected from the pre-screening step and included in the main screening of 104 NF1 sera, which confirmed IGFBP1 and TNF-α, and identified four new proteins (interleukin (IL)-6, interferon (IFN)-γ, epidermal growth factor receptor (EGFR), and Regulated upon activation, normal T-cell expressed and secreted (RANTES)) as potential biomarkers.