Dataset Information

Human, bronchoalveolar lavage, extracellular vesicles

ABSTRACT: The aim of the project was to explore large extracellular vesicles capacity to seperate non lung cancer from lung cancer cases. A case control study of patients suspected for lung cancer (12 non lung cancer and 12 lung cancers). The raw files are labeled according to clinical status. Small and large extracellular vesicles were isolated by differential centrifugation. The proteome of full BAL, vesicle depleted BAL, small and large extracellular vesicles were characterized by LC-MS. Small extracellular vesicles were further analyzed by nanoparticle tracking analysis, Transmission electron microscopy and western blots.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, T Cell, Lung, Macrophage

DISEASE(S): Lung Cancer

SUBMITTER: Rune Matthiesen

LAB HEAD: Rune Matthiesen

PROVIDER: PXD021988 | Pride | 2020-12-15

REPOSITORIES: Pride

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Publications

Is the Proteome of Bronchoalveolar Lavage Extracellular Vesicles a Marker of Advanced Lung Cancer?

Carvalho Ana Sofia AS Moraes Maria Carolina Strano MCS Hyun Na Chan C Fierro-Monti Ivo I Henriques Andreia A Zahedi Sara S Bodo Cristian C Tranfield Erin M EM Sousa Ana Laura AL Farinho Ana A Rodrigues Luís Vaz LV Pinto Paula P Bárbara Cristina C Mota Leonor L Abreu Tiago Tavares de TT Semedo Júlio J Seixas Susana S Kumar Prashant P Costa-Silva Bruno B Pandey Akhilesh A Matthiesen Rune R

Cancers 20201120 11

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 initiati ...[more]

PMID: 33233545

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Project description:Segmental instillation of lipopolysaccharide (LPS) by bronchoscopy can be used as a model to safely induce transient airway inflammation in the human lung. The LPS challenge model enables investigation of cellular mechanisms involved in pulmonary inflammatory processes as well as pharmacodynamic analysis of investigational drugs for the treatment of respiratory diseases. Aim of this work was to describe the transcriptomic profile of the human segmental LPS challenge model with contextualization to major respiratory diseases. Pre-challenge bronchoalveolar lavage fluid (BAL) and biopsies were sampled from twenty-eight smoking, healthy subjects, followed by segmental LPS challenge and saline control challenge. Twenty-four hours post instillation, BAL and biopsies were collected from the challenged lung segments. Total RNA of cells from BAL and biopsy samples were sequenced for subsequent data analysis. Differential gene expression analysis resulted in 6316 upregulated differentially expressed genes (DEGs) and 241 downregulated DEG in BAL, but only one downregulated DEG in biopsy samples after LPS challenge compared to saline challenge. Upregulated DEG in BAL were related to molecular functions such as “Inflammatory response” or “antimicrobial humoral immune response mediated by antimicrobial peptide”, enriched biological processes such as “chemokine receptor activity”, and upregulated pro-inflammatory pathways such as “Wnt signaling pathway”, “Ras signaling pathway” or “JAK-STAT signaling pathway”. Furthermore, the segmental LPS challenge model resembled aspects of the five most prevalent respiratory diseases chronic obstructive pulmonary disease (COPD), asthma, pneumonia, tuberculosis and lung cancer and featured similarities with acute exacerbations in COPD (AECOPD) and community-acquired pneumonia (CAP). Overall, our study provides extensive information about the transcriptomic profile from BAL cells and mucosal biopsies following LPS challenge in healthy smokers. It expands the knowledge about the LPS challenge model providing potential overlap with respiratory diseases in general and infection-triggered respiratory insults such as AECOPD in particular.

			Action	DRS
	DB_sQ27_No.mgf	Mgf
	DB_sQ27_No.raw	Raw
	DB_sQ27_No.txt	Txt
	DB_sQ57_Yes.mgf	Mgf
	DB_sQ57_Yes.raw	Raw