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 < 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.
Highlights
Hepatocellular carcinoma (HCC) is the second highest cause of tumour-related death worldwide [1]
This study suggests that serum exosomal miR-665 may be a novel minimally invasive biomarker for hepatocellular carcinoma (HCC) diagnosis and prognosis
By detecting miR-665 expression levels in exosomes separated from the serum of HCC patients and healthy controls, we further explore the value of exosomal miR-665 in the early diagnosis and prognosis of HCC
Summary
Hepatocellular carcinoma (HCC) is the second highest cause of tumour-related death worldwide [1]. Combined with the high invasion and metastasis degree of HCC, the prognosis of HCC patients is extremely poor [2, 3]. It is of great significance to identify sensitive and specific markers for the early diagnosis of HCC. Accumulating evidence indicates that miRNAs are involved in the proliferation, metastasis and angiogenesis of tumour cells [5]. MiRNAs are highly expressed in the serum of patients with many types of tumours, such as HCC [6], colorectal cancer [7], and pancreatic cancer [8], suggesting that miRNA expression in serum may be a new www.impactjournals.com/oncotarget non-invasive marker for the diagnosis of multiple tumours, including HCC Accumulating evidence indicates that miRNAs are involved in the proliferation, metastasis and angiogenesis of tumour cells [5]. miRNAs are highly expressed in the serum of patients with many types of tumours, such as HCC [6], colorectal cancer [7], and pancreatic cancer [8], suggesting that miRNA expression in serum may be a new www.impactjournals.com/oncotarget non-invasive marker for the diagnosis of multiple tumours, including HCC
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