TY - JOUR T1 - Proteomics of serum extracellular vesicles identifies a novel COPD biomarker, fibulin-3 from elastic fibres JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00658-2020 VL - 7 IS - 1 SP - 00658-2020 AU - Taro Koba AU - Yoshito Takeda AU - Ryohei Narumi AU - Takashi Shiromizu AU - Yosui Nojima AU - Mari Ito AU - Muneyoshi Kuroyama AU - Yu Futami AU - Takayuki Takimoto AU - Takanori Matsuki AU - Ryuya Edahiro AU - Satoshi Nojima AU - Yoshitomo Hayama AU - Kiyoharu Fukushima AU - Haruhiko Hirata AU - Shohei Koyama AU - Kota Iwahori AU - Izumi Nagatomo AU - Mayumi Suzuki AU - Yuya Shirai AU - Teruaki Murakami AU - Kaori Nakanishi AU - Takeshi Nakatani AU - Yasuhiko Suga AU - Kotaro Miyake AU - Takayuki Shiroyama AU - Hiroshi Kida AU - Takako Sasaki AU - Koji Ueda AU - Kenji Mizuguchi AU - Jun Adachi AU - Takeshi Tomonaga AU - Atsushi Kumanogoh Y1 - 2021/01/01 UR - http://openres.ersjournals.com/content/7/1/00658-2020.abstract N2 - There is an unmet need for novel biomarkers in the diagnosis of multifactorial COPD. We applied next-generation proteomics to serum extracellular vesicles (EVs) to discover novel COPD biomarkers.EVs from 10 patients with COPD and six healthy controls were analysed by tandem mass tag-based non-targeted proteomics, and those from elastase-treated mouse models of emphysema were also analysed by non-targeted proteomics. For validation, EVs from 23 patients with COPD and 20 healthy controls were validated by targeted proteomics.Using non-targeted proteomics, we identified 406 proteins, 34 of which were significantly upregulated in patients with COPD. Of note, the EV protein signature from patients with COPD reflected inflammation and remodelling. We also identified 63 upregulated candidates from 1956 proteins by analysing EVs isolated from mouse models. Combining human and mouse biomarker candidates, we validated 45 proteins by targeted proteomics, selected reaction monitoring. Notably, levels of fibulin-3, tripeptidyl-peptidase 2, fibulin-1, and soluble scavenger receptor cysteine-rich domain-containing protein were significantly higher in patients with COPD. Moreover, six proteins; fibulin-3, tripeptidyl-peptidase 2, UTP-glucose-1-phosphate uridylyl transferase, CD81, CD177, and oncoprotein-induced transcript 3, were correlated with emphysema. Upregulation of fibulin-3 was confirmed by immunoblotting of EVs and immunohistochemistry in lungs. Strikingly, fibulin-3 knockout mice spontaneously developed emphysema with age, as evidenced by alveolar enlargement and elastin destruction.We discovered potential pathogenic biomarkers for COPD using next-generation proteomics of EVs. This is a novel strategy for biomarker discovery and precision medicine.This study identified novel biomarkers for COPD using next-generation proteomics of serum extracellular vesicles. Notably, the expression of fibulin-3 is correlated with lung function and emphysema. This could be useful for personalised medicine. https://bit.ly/2JfRCgk ER -