Proteomic profiling identifies co-regulated expression of splicing factors as a characteristic feature of intravenous leiomyomatosis
Krasny, Lukas Wilding, Chris P Perkins, Emma Arthur, Amani Guljar, Nafia Jenks, Andrew D Fisher, Cyril Judson, Ian Thway, Khin Jones, Robin L
Krasny, Lukas
Wilding, Chris P
Perkins, Emma
Arthur, Amani
Guljar, Nafia
Jenks, Andrew D
Fisher, Cyril
Judson, Ian
Thway, Khin
Jones, Robin L
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Affiliation
The Institute of Cancer Research; The Royal Marsden NHS Foundation Trust; University Hospitals Birmingham NHS Foundation Trust
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Publication date
2022-06-13
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Abstract
Intravenous leiomyomatosis (IVLM) is a rare benign smooth muscle tumour that is characterised by intravenous growth in the uterine and pelvic veins. Previous DNA copy number and transcriptomic studies have shown that IVLM harbors unique genomic and transcriptomic alterations when compared to uterine leiomyoma (uLM), which may account for their distinct clinical behaviour. Here we undertake the first comparative proteomic analysis of IVLM and other smooth muscle tumours (comprising uLM, soft tissue leiomyoma and benign metastasizing leiomyoma) utilising data-independent acquisition mass spectrometry. We show that, at the protein level, IVLM is defined by the unique co-regulated expression of splicing factors. In particular, IVLM is enriched in two clusters composed of co-regulated proteins from the hnRNP, LSm, SR and Sm classes of the spliceosome complex. One of these clusters (Cluster 3) is associated with key biological processes including nascent protein translocation and cell signalling by small GTPases. Taken together, our study provides evidence of co-regulated expression of splicing factors in IVLM compared to other smooth muscle tumours, which suggests a possible role for alternative splicing in the pathogenesis of IVLM.
Citation
Krasny L, Wilding CP, Perkins E, Arthur A, Guljar N, Jenks AD, Fisher C, Judson I, Thway K, Jones RL, Huang PH. Proteomic Profiling Identifies Co-Regulated Expression of Splicing Factors as a Characteristic Feature of Intravenous Leiomyomatosis. Cancers (Basel). 2022 Jun 13;14(12):2907. doi: 10.3390/cancers14122907.
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Article