ArticleResearch square2025
Single-cell tumor microenvironment profiling informs a circulating proteome test for the interception of malignant transformation in NF1 nerve sheath tumors.
Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The most common cause of death in neurofibromatosis type 1 (NF1) is the development of malignant peripheral nerve sheath tumor (MPNST), a deadly sarcoma that can transform from benign plexiform neurofibromas (PN) or premalignant atypical neurofibromas (AN). We built a single-cell dataset of 55 NF1-associated PN, AN, and MPNST to define cellular changes in neurofibroma at-risk of malignant transformation. Integrative analysis of changes in the tumor microenvironment revealed the emergence of malignant tumor cells, regulatory T cells, and loss of activated macrophages in MPNST. Using this reference dataset, we validated findings using anchor-based label transfer in an additional 19 NF1 nerve sheath tumors profiled with single cell sequencing, and public datasets. We then defined protein biomarkers of malignant transformation from high-throughput proteomic analysis of plasma samples collected from 45 NF1 patients that correlated to mRNAs specific to MPNST cell populations. Fifty plasma proteins accurately and non-invasively distinguished patients with MPNST from those with premalignant tumors. These markers should improve the ability to identify high-risk neurofibromas for improved cancer surveillance and enable early detection of malignant transformation in NF1.
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