Abstract 5441: Circulating exosomal microRNA-203 and microRNA-373 as non-invasive biomarkers for predicting prognosis and metastasis in human hepatocellular carcinoma

Abstract

Abstract Background and Aim Hepatocellular carcinoma (HCC) is the fifth most common cancer and the most leading cause of cancer-related death worldwide. Although considerable progress has been made in treatment of HCC, early detection is still highly considered the key to improved survival. Thus, for the earlier diagnosis and accurate prediction of HCC, identification of non-invasive molecular biomarkers for HCC patients is an imperative need. Recently, cancer cell-derived extracellular vesicles (EVs) have been known to contain various intracellular biomolecules including microRNAs (miRNAs). The aim of this study was to evaluate whether exosomal miRNAs can serve as a serum-based biomarker in HCC. Materials and Methods We isolated exosome from serum samples from HCC patients as well as normal healthy controls using ultracentrifugation, and it was confirmed by expression of exosome markers (CD9, CD63, ALIX, and TSG101) based on immunoblotting. Next, the expression of 6 miRNAs (miRNA-24, -130a, -182, -203, -373, and -423) was analyzed in the exosome samples. We also investigated expression status of the 6 miRNAs in matched HCC tissues and corresponding normal liver tissues. MiRNAs expression was determined by quantitative real-time PCR (qRT-PCR), and miRNAs expression was normalized relative to cel-miR-39 and RNU6B expression for serum and tissue samples, respectively. Results We successfully purified exosome from serum clinical samples and detected miRNAs in the exosome. We observed that a subset of miRNAs from serum exosome, including miRNA-24, -130a, -182, -203, and -373 were enhanced in HCC patients than normal healthy controls. In further comparison between early stage and advanced stage of HCC patients, serum exosomal miRNA-203 (P<0.05) and miRNA-373 (P<0.05) were significantly up-regulated in advanced HCC patients. While no significant changes in the expression of other serum exosomal miRNAs (miRNA-24, -130a, -182, and -423) according to HCC progression. More interestingly, high serum exosomal miRNA-203 and miRNA-373 was associated with HCC progression (P<0.01) as well as prognosis (P<0.05) of HCC patients. Conclusions We provided the novel evidence for usefulness of serum circulating exosomal miR-203 and miR-373 expressions as strong potential biomarkers for predicting prognosis and metastasis of HCC patients. Citation Format: Gyeonghwa Kim, Eunhye Lee, Se Young Jang, Won Young Tak, Young Oh Kweon, Soo Young Park, Keun Hur. Circulating exosomal microRNA-203 and microRNA-373 as non-invasive biomarkers for predicting prognosis and metastasis in human hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5441. doi:10.1158/1538-7445.AM2017-5441