Proteomic Profiling Identifies Co-Regulated Expression of Splicing Factors as a Characteristic Feature of Intravenous Leiomyomatosis

Cancers

Amani Arthur¹  Nafia Guljar¹  Andrew D. Jenks¹  Emma Perkins¹  Paul H. Huang¹  Chris P. Wilding¹  Khin Thway¹  Lukas Krasny¹  Robin L. Jones²  Ian Judson²  Cyril Fisher³ 

[1] Division of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UK;The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK;University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK;

关键词: proteomics;    spliceosome;    splicing factors;    leiomyoma;    intravenous leiomyomatosis;   

DOI  :  10.3390/cancers14122907

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown