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

被引：19

作者：

Carvalho, Ana Sofia ^{[1
]}

Moraes, Maria Carolina Strano ^{[2
]}

Hyun Na, Chan ^{[3
]}

Fierro-Monti, Ivo ^{[1
]}

Henriques, Andreia ^{[1
]}

Zahedi, Sara ^{[1
]}

Bodo, Cristian ^{[2
]}

Tranfield, Erin M. ^{[4
]}

Sousa, Ana Laura ^{[4
]}

Farinho, Ana ^{[5
]}

Rodrigues, Luis Vaz ^{[6
]}

Pinto, Paula ^{[7
]}

Barbara, Cristina ^{[8
]}

Mota, Leonor ^{[7
]}

de Abreu, Tiago Tavares ^{[7
]}

Semedo, Julio ^{[7
]}

Seixas, Susana ^{[9
]}

Kumar, Prashant ^{[10
,11
]}

Costa-Silva, Bruno ^{[2
]}

Pandey, Akhilesh ^{[10
,11
,12
]}

Matthiesen, Rune ^{[1
]}

机构：

[1] Univ Nova Lisboa, NOVA Med Sch, Computat & Expt Biol Grp, Fac Ciencias Med,Chron Dis Res Ctr, Campo Martires da Patria 130, P-1169056 Lisbon, Portugal

[2] Champalimaud Ctr Unknown, Syst Oncol Grp, Champalimaud Res, Av Brasilia, P-1400038 Lisbon, Portugal

[3] Johns Hopkins Univ, Sch Med, Dept Neurol, Inst Cell Engn, Baltimore, MD 21205 USA

[4] Inst Gulbenkian Ciencias, Electron Microscopy Facil, Rua da Quinta Grande 6, P-2780156 Oeiras, Portugal

[5] Univ Nova Lisboa, NOVA Med Sch, CEDOC Chron Dis Res Ctr, iNOVA4Hlth Adv Precis Med,Fac Ciencias Med, Campo Martires da Patria 130, P-1169056 Lisbon, Portugal

[6] Unidade Local Saude Guarda USLGuarda, Dept Pneumol, P-6300659 Guarda, Portugal

[7] Ctr Hosp Lisboa Norte, Hosp Pulido Valente, Unidade Tecn Invas Pneumol 2, Pneumol 2, P-1649028 Lisbon, Portugal

[8] Univ Lisbon, Inst Saude Ambiental ISAMB, Ctr Hosp Univ Lisboa Norte, Fac Med, P-1649028 Lisbon, Portugal

[9] Univ Porto, Inst Invest & Inovacao Saude I3S, P-4200135 Porto, Portugal

[10] ITPL, Inst Bioinformat, Discoverer Bldg, Bangalore 560066, Karnataka, India

[11] Manipal Acad Higher Educ MAHE, Manipal 576104, India

[12] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA

来源：

CANCERS | 2020年 / 12卷 / 11期

基金：

英国惠康基金;

关键词：

extracellular vesicles; lung cancer; proteomics; immuno oncology; bronchoalveolar lavage; CELLS; FLUID; IDENTIFICATION; METHYLATION; BIOMARKERS; INTEGRINS; PATHWAY;

D O I：

10.3390/cancers12113450

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary 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 analyzed 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. 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.

引用

页码：1 / 18

页数：18