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

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.

CD5L as an Extracellular Vesicle-Derived Biomarker for Liquid Biopsy of Lung Cancer

“…This result indicated that CLEC3B, ITIH4, SERFINF1, SAA4, SERFINC1, and C20ORF3 cannot serve as effective biomarkers for lung cancer. CD5L was also detected in the EVs from bronchoalveolar lavage of lung cancer patients, but there was no correlation to the tumor progress [ 28 ]. It is attributed to the different sample numbers ( n = 24 for bronchoalveolar lavage) to our study ( n = 80), the different isolation methods used in the two studies (ultracentrifugation vs. magnetic separation), and the difference in the sample origin.…”

EVs from BALF—Mediators of Inflammation and Potential Biomarkers in Lung Diseases

“…Both pathways were described as involved in cancer promotion [ 99 , 100 ]. Researchers selected also the protein DNA (cytosine-5)-methyltransferase 3β (DNMT3B) complex as significantly upregulated in BALF-EVs from lung cancer patients [ 101 ]. The DNMT3B complex is responsible for de novo epigenetic modifications and considered as a prospective therapeutic target [ 102 ].…”

Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping

“…The possibility to diagnose and screen DLBCL patients for treatment based on liquid biopsies by targeting the proteome of extracellular vesicles (EVs) is unexplored and provides clear advantages. Minimally invasive liquid biopsy-based diagnosis and patient screen opens new avenues for fast and longitudinal follow up for minimal residual disease assessment [11,12].…”

“…EVs have attracted much recent interest because of their potential functions, use as disease biomarkers, and possible therapeutic exploitation [12,13]. EVs are extracellular vesicles of endosomal and plasma membrane origin released in vivo into the extracellular environment by cells as distinct as B lymphocytes and dendritic cells as well as from several additional cell types of hematopoietic origin [14].…”