Is the proteome of bronchoalveolar lavage extracellular vesicles a marker of advanced lung cancer?

• Published in: Cancers 2020, Vol.12 (11), p.3450
• Main Authors: Carvalho, Ana Sofia, Moraes, Maria Carolina Strano, Hyun Na, Chan, Fierro-Monti, Ivo, Henriques, Andreia, Zahedi, Sara, Bodo, Cristian, Tranfield, Erin M, Sousa, Ana Laura, Farinho, Ana, Rodrigues, Luís Vaz, Pinto, Paula Maria Gonçalves, Bárbara, Cristina, Mota, Leonor, Abreu, Tiago Tavares de, Semedo, Júlio, Seixas, Susana, Kumar, Prashant, Costa-Silva, Bruno, Pandey, Akhilesh, Matthiesen, Rune
• Format: Article
• Language: English
• Subjects: Bronchoalveolar lavage; Extracellular vesicles; Immuno oncology; Lung cancer; Proteomics
• ISSN: 2072-6694
• DOI: 10.3390/cancers12113450

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking status and gender. Despite these advances BAL small and large extracellular vehicles (EVs) proteomes reveal aberrant protein expression in paracrine signaling mechanisms in cancer initiation and progression. We consequently present a case-control study of 24 bronchoalveolar lavage extracellular vesicle samples which were analyzed by state-of-the-art liquid chromatography-mass spectrometry (LC-MS). We obtained evidence that BAL EVs proteome complexity correlated with lung cancer stage 4 and mortality within two years´ follow-up (p value = 0.006). The potential therapeutic target DNMT3B complex is significantly up-regulated in tumor tissue and BAL EVs. The computational analysis of the immune and fibroblast cell markers in EVs suggests that patients who deceased within the follow-up period display higher marker expression indicative of innate immune and fibroblast cells (four out of five cases). This study provides insights into the proteome content of BAL EVs and their correlation to clinical outcomes. R.M. is supported by Fundação para a Ciência e a Tecnologia (CEEC position, 2019–2025 investigator).This article is a result of the projects (iNOVA4Health—UID/Multi/04462/2013), supported by Lisboa PortugalRegional Operational Programme (Lisboa2020), under the PORTUGAL 2020 Partnership Agreement, through theEuropean Regional Development Fund (ERDF). This work is also funded by FEDER funds through the COMPETE2020 Programme and National Funds through FCT—Portuguese Foundation for Science and Technology underthe projects number PTDC/BTM-TEC/30087/2017 and PTDC/BTM-TEC/30088/2017. This work was supported bythe Wellcome Trust/DBT India Alliance Margdarshi Fellowship (grant number IA/M/15/1/502023) awarded to A.P.B.C.-S., M.C.S.C. and C.B. are supported by the Champalimaud Foundation and the EMBO Installation Grant 3921