Lung cancer bronchoalveolar lavage: proteome landscape of extracellular vesicles, a cue to diagnosis

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Lung cancer bronchoalveolar lavage: proteome landscape of extracellular vesicles, a cue to diagnosis

Wednesday, 10.02.2021

Bronchoalveolar lavage is routinely collected during bronchoscopy for cytology analysis in the diagnostic of lung cancer. Due to low sensitivity of this method, early-stage cancers are undetected, lowering the treatment success. In this study, we analysed extracellular vesicles isolated from bronchoalveolar lavage of lung cancer suspects by mass spectrometry-based proteomics. The protein composition of bronchoalveolar lavage extracellular vesicles of late-stage cancer showed a higher proteome complexity associated with mortality within the two year follow-up period. We identified a potential therapeutic target DNMT3B complex which was significantly expressed in bronchoalveolar lavage extracellular vesicles as well as in tumor tissue. Bronchoalveolar lavage extracellular vesicles proteome analysis of immune markers indicates the presence of markers of innate immune and fibroblast cells.

 

Authors and Affiliations:

Ana Sofia Carvalho1,*, Maria Carolina Strano Moraes2, Chan Hyun Na3, Ivo Fierro-Monti1, Andreia Henriques1, Sara Zahedi1 , Cristian Bodo2 , Erin M Tranfield4 , Ana Laura Sousa4,  Ana Farinho5 , Luís Vaz Rodrigues6 , Paula Pinto7 , Cristina Bárbara8 , Leonor Mota7 , Tiago Tavares de Abreu7 , Júlio Semedo7 , Susana Seixas9 , Prashant Kumar10,11 , Bruno Costa-Silva2, Akhilesh Pandey10,11,12 and Rune Matthiesen 1,*

1 Computational and Experimental Biology Group, Chronic Diseases Research Centre, NOVA Medical School, Faculdade de Ciencias Medicas, Universidade NOVA de Lisboa, Campo dos Martires da Patria, 130, 1169-056 Lisboa, Portugal

Systems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown, Av. Brasilia, Doca de Pedroucos, 1400-038 Lisbon, Portugal

Department of Neurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

Electron Microscopy Facility, Instituto Gulbenkian de Ciência—Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal

iNOVA4Health—Advancing Precision Medicine, CEDOC—Chronic Diseases Research Centre, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Martires da Patria, 130, 1169-056 Lisboa, Portugal

Department of Pneumology, Unidade Local de Saúde da Guarda (USLGuarda), 6300-659 Guarda, Portugal

Unidade de Técnicas Invasivas Pneumológicas, Pneumologia II, Hospital Pulido Valente, Centro Hospitalar Lisboa Norte, 1649-028 Lisbon, Portugal

Instituto de Saúde Ambiental (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Centro Hospitalar Universitário Lisboa Norte, 1649-028 Lisbon, Portugal

Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, 4200-135 Porto, Portugal

10 Institute of Bioinformatics, Discoverer building, ITPL, Bangalore 560066, India

11 Manipal Academy of Higher Education (MAHE), Manipal 576104, India

12 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA

*Authors to whom correspondence should be addressed.

 

Abstract:

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.

 

Journal: Cancers

 

Link: https://www.mdpi.com/2072-6694/12/11/3450