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

Ana Sofia Carvalho, Maria Carolina Strano Moraes, Chan Hyun Na, Ivo Fierro-Monti, Andreia Henriques, Sara Zahedi, Cristian Bodo, Erin M. Tranfield, Ana Laura Sousa, Ana Farinho, Luís Vaz Rodrigues, Paula Pinto, Cristina Bárbara, Leonor Mota, Tiago Tavares de Abreu, Júlio Semedo, Susana Seixas, Prashant Kumar, Bruno Costa-Silva, Akhilesh PandeyRune Matthiesen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number3450
Pages (from-to)1-18
Number of pages18
JournalCancers
Volume12
Issue number11
DOIs
StatePublished - Nov 2020

Keywords

  • Bronchoalveolar lavage
  • Extracellular vesicles
  • Immuno oncology
  • Lung cancer
  • Proteomics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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