Exosomal miR-665 as a novel minimally invasive biomarker for hepatocellular carcinoma diagnosis and prognosis

// Zhen Qu 1, 3, * , Junhua Wu 2, * , Junyi Wu 1, 2 , Anlai Ji 4, 5 , Guanghui Qiang 2, 5 , Yong Jiang 3 , Chunping Jiang 1 and Yitao Ding 1 1 Department of Hepatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China 2 Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu Province, China 3 Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China 4 Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China 5 Department of Hepatobiliary Surgery, Drum Tower Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China * These authors contributed equally to this work Correspondence to: Yong Jiang, email: yjiang8888@hotmail.com Chunping Jiang, email: chunpingjiang@163.com Yitao Ding, email: drdingyitao0@sina.com Keywords: HCC, exosomal miRNA-665, biomarker, ERK, tumor growth Received: April 13, 2017      Accepted: August 26, 2017      Published: September 14, 2017 ABSTRACT Recent studies have shown that circulating microRNAs are potential biomarkers for various types of malignancies. The aim of this study was to investigate the feasibility of using serum exosomal microRNAs (miRNAs) as novel serological biomarkers for hepatocellular carcinoma (HCC) diagnosis and prognosis. Exosomes are small membranous vesicles (30–100 nm). Exosomal miR-665 levels in HCC patients were significantly higher than those in healthy subjects ( P 5 cm), in tumours with local invasion and in those at an advanced clinical stage (stage III/IV) of HCC ( P = 0.0042, 0.0197, and 0.0276, respectively). The survival time of the exosomal miR-665 high-expression group ( n = 17) was significantly shorter than that of the low-expression group ( n = 13) ( P = 0.036). In addition, we found that HCC cell-derived exosomes promoted hepatoma cell proliferation and upregulated the expression level of proteins in the MAPK/ERK pathway in vitro and in vivo . This study suggests that serum exosomal miR-665 may be a novel minimally invasive biomarker for HCC diagnosis and prognosis.