The Deep Proteomics Approach Identified Extracellular Vesicular Proteins Correlated to Extracellular Matrix in Type One and Two Endometrial Cancer

深度蛋白质组学方法鉴定出与一型和二型子宫内膜癌细胞外基质相关的细胞外囊泡蛋白

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作者:Valeria Capaci, Feras Kharrat, Andrea Conti, Emanuela Salviati, Manuela Giovanna Basilicata, Pietro Campiglia, Nour Balasan, Danilo Licastro, Federica Caponnetto, Antonio Paolo Beltrami, Lorenzo Monasta, Federico Romano, Giovanni Di Lorenzo, Giuseppe Ricci, Blendi Ura

Abstract

Among gynecological cancers, endometrial cancer is the most common in developed countries. Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that contain proteins involved in immune response and apoptosis. A deep proteomic approach can help to identify dysregulated extracellular matrix (ECM) proteins in EVs correlated to key pathways for tumor development. In this study, we used a proteomics approach correlating the two acquisitions-data-dependent acquisition (DDA) and data-independent acquisition (DIA)-on EVs from the conditioned medium of four cell lines identifying 428 ECM proteins. After protein quantification and statistical analysis, we found significant changes in the abundance (p < 0.05) of 67 proteins. Our bioinformatic analysis identified 26 pathways associated with the ECM. Western blotting analysis on 13 patients with type 1 and type 2 EC and 13 endometrial samples confirmed an altered abundance of MMP2. Our proteomics analysis identified the dysregulated ECM proteins involved in cancer growth. Our data can open the path to other studies for understanding the interaction among cancer cells and the rearrangement of the ECM.

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