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- W2289059479 abstract "Bone Morphogenic Protein 2 (BMP2) is a multipurpose cytokine, important in the development of bone and cartilage, and with a role in tumour initiation and progression. Because of BMP2’s osteogenic properties, a recombinant human version (rhBMP2) has found utility as an adjuvant therapy during surgery for spinal fusions. However, the results of large-scale meta-analysis has highlighted the potential of rhBMP2 to promote new tumour formation, leading to an FDA black box warning. BMP2 signal transduction is dependent on two distinct classes of serine/threonine kinase known as the type I and type II receptors. Although the type I receptors (BMPR1A and BMPR1B) are largely thought to have overlapping functions, we find tissue and cellular compartment specific patterns of expression, suggesting potential for distinct BMP2 signalling outcomes dependent on tissue type. Herein, we utilise large publicly available datasets from The Cancer Genome Atlas (TCGA) and Protein Atlas to define a novel role for BMPR1A-biased BMP2 signalling in soft tissue sarcomas. Using disease free survival as our primary endpoint, we find this BMPR1A-biased BMP2 signalling confers poor overall prognosis compared both to patients with BMPR1B-biased and to the sarcoma dataset as a whole. Through further annotation of the TCGA sarcoma dataset, we localise this effect to dedifferentiated liposarcomas but find overall BMP2/BMP receptor expression is equal across subsets. Finally, through gene set enrichment analysis we link this effect to increased transcriptional activity of the matrisome and general extracellular matrix remodelling. Our study highlights the importance of continued research into the tumorigenic properties of BMP2, the need for extensive patient follow-up and the potential disadvantages of rhBMP2 use. For the first time, we identify BMPR1A-biased BMP2 signalling as a biomarker of disease relapse in dedifferentiated liposarcomas." @default.
- W2289059479 created "2016-06-24" @default.
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- W2289059479 date "2016-02-06" @default.
- W2289059479 modified "2023-09-27" @default.
- W2289059479 title "BMPR1A signalling is linked to tumour progression in dedifferentiated liposarcomas: lessons for rhBMP2 use in spinal surgery" @default.
- W2289059479 doi "https://doi.org/10.7287/peerj.preprints.1719v1" @default.
- W2289059479 hasPublicationYear "2016" @default.
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