Plasma-derived extracellular vesicle proteins as a source of biomarkers for lung adenocarcinoma
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Jody Vykoukal1,5, Nan Sun1, Clemente Aguilar-Bonavides2, Hiroyuki Katayama1, Ichidai Tanaka3, Johannes F. Fahrmann1, Michela Capello1, Junya Fujimoto3, Mitzi Aguilar1, Ignacio I. Wistuba3, Ayumu Taguchi3, Edwin J. Ostrin4 and Samir M. Hanash1,3,5
1Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA
2Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA
3Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA
4Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA
5McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA
Samir M. Hanash, email: firstname.lastname@example.org
Keywords: extracellular vesicles and exosomes; proteomics; liquid biopsy; lung cancer; biomarker discovery
Received: March 22, 2017 Accepted: August 02, 2017 Published: September 08, 2017
Exosomes and other extracellular vesicles (EVs) have been implicated as mediators of intercellular communication. Their release into the circulation has the potential to inform about tumor status. In-depth proteomic characterization of plasma-derived EVs has been limited by challenges in isolating EVs from protein-abundant biological fluids. We implemented a novel single-step density gradient flotation workflow for efficient and rapid isolation of highly enriched circulating EVs from plasma. Mass-spectrometry analysis of plasma EVs from subjects with lung adenocarcinoma and matched controls resulted in the identification of 640 proteins. A total of 108 proteins exhibited significant (p<0.05) differential expression in vesicle preparations derived from lung adenocarcinoma case plasmas compared to controls, of which 43 were also identified in EVs from lung adenocarcinoma cell lines. Four top performing EV-associated proteins that distinguished adenocarcinoma cases from controls, SRGN, TPM3, THBS1 and HUWE1, yielded a combined area under the receiver operating characteristic curve (AUC) of 0.90 (95% CI = 0.76-1). Our findings support the potential of EV derived proteins as a source of biomarkers that complement other approaches for tumor assessment.
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