Exosomal miR-665 as a novel minimally invasive biomarker for hepatocellular carcinoma diagnosis and prognosis
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Zhen Qu1,3,*, Junhua Wu2,*, Junyi Wu1,2, Anlai Ji4,5, Guanghui Qiang2,5, Yong Jiang3, Chunping Jiang1 and Yitao Ding1
1Department of Hepatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China
2Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu Province, China
3Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China
4Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, China
5Department of Hepatobiliary Surgery, Drum Tower Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China
*These authors contributed equally to this work
Yong Jiang, email: [email protected]
Chunping Jiang, email: [email protected]
Yitao Ding, email: [email protected]
Keywords: HCC, exosomal miRNA-665, biomarker, ERK, tumor growth
Received: April 13, 2017 Accepted: August 26, 2017 Published: September 14, 2017
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 < 0.05), and exosomal miR-665 levels were significantly upregulated in tumours larger in size (> 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.
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