Krasny Lukas, Wilding Chris P, Perkins Emma, Arthur Amani, Guljar Nafia, Jenks Andrew D, Fisher Cyril, Judson Ian, Thway Khin, Jones Robin L, Huang Paul H
Division of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UK.
The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
Cancers (Basel). 2022 Jun 13;14(12):2907. doi: 10.3390/cancers14122907.
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.
静脉内平滑肌瘤病（IVLM）是一种罕见的良性平滑肌肿瘤，其特征是在子宫和盆腔静脉内生长。先前的DNA拷贝数和转录组学研究表明，与子宫平滑肌瘤（uLM）相比，IVLM具有独特的基因组和转录组改变，这可能解释了它们不同的临床行为。在此，我们利用数据非依赖采集质谱法对IVLM和其他平滑肌肿瘤（包括uLM、软组织平滑肌瘤和良性转移性平滑肌瘤）进行了首次比较蛋白质组学分析。我们发现，在蛋白质水平上，IVLM由剪接因子的独特共调控表达所定义。特别是，IVLM在由剪接体复合物的hnRNP、LSm、SR和Sm类共调控蛋白组成的两个簇中富集。其中一个簇（簇3）与关键生物学过程相关，包括新生蛋白转运和小GTP酶介导的细胞信号传导。综上所述，我们的研究提供了证据，表明与其他平滑肌肿瘤相比，IVLM中存在剪接因子的共调控表达，这提示可变剪接在IVLM发病机制中可能起作用。
