Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer

Abstract

// Qingyun Liu 1, * , Zubin Yu 2, * , Shuai Yuan 1, * , Weijia Xie 1 , Chengying Li 1 , Zeyao Hu 1 , Ying Xiang 1 , Na Wu 1 , Long Wu 1 , Li Bai 3, ** , Yafei Li 1, ** 1 Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, People’s Republic of China 2 Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China 3 Department of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China * These authors have contributed equally to this work ** These authors jointly directed the project Correspondence to: Yafei Li, email: liyafei2008@hotmail.com Keywords: non-small-cell lung cancer (NSCLC), exosome, miRNAs, prognosis, biomarker Received: June 29, 2016 Accepted: December 05, 2016 Published: December 30, 2016 ABSTRACT Exosomal miRNAs are proposed as excellent candidate biomarkers for clinical applications. However, little is known about their potential roles as prognostic biomarkers in lung cancer. In this study, we explored the prognostic value of plasma exosomal microRNAs (miRNAs) for non-small-cell lung cancer (NSCLC). Using a quantitative polymerase chain reaction (qPCR) array panel, we analyzed 84 plasma exosomal miRNAs in 10 lung adenocarcinoma patients and 10 matched healthy controls. The qPCR array showed 30 aberrantly expressed exosomal miRNAs. Nine candidate miRNAs were selected based on differential expression and previous reports for further evaluating their prognostic roles in 196 NSCLC patients. Elevated levels of exosomal miR-23b-3p, miR-10b-5p and miR-21-5p were independently associated with poor overall survival (with hazard ratio [95% confidence interval]: 2.42 (1.45 - 4.04), P = 0.001; 2.22 (1.18 - 4.16), P = 0.013; 2.12 (1.28 - 3.49), P = 0.003, respectively). When compared to the clinical prognostic variables only model, adding the three exosomal miRNA signatures significantly improved survival predictive accuracy with an increase of time-dependent area under the receiver operating characteristic curve from 0.88 to 0.91 (P=0.015). Our results indicated that plasma exosomal miR-23b-3p, miR-10b-5p and miR-21-5p are promising non-invasive prognostic biomarkers of NSCLC.