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IDDF2019-ABS-0167 Identification of cancer-related exosomal mirnas in NASH-induced liver cirrhosis with hepatocellular carcinoma

Background The objective of this study was to identify the presence of selected miRNAs in exosomes of the serum and ascitic fluid and to determine their expression levels in patients with NASH-related liver cirrhosis with or without HCC Methods A literature search was performed to identify potential miRNAs involved in the pathogenesis of HCC. The expression of the miRNA candidates in the exosome of serum and ascitic fluid were investigated in 52 patients of NASH-induced liver cirrhosis with HCC (n=26) as compared to NASH-induced liver cirrhosis without HCC (n=26) by using quantitative real-time PCR. Fold change was calculated using 2^- ΔΔCTmethod. Results The median age for patients with NASH-induced liver cirrhosis with HCC was 71.5 years old versus the control group of 60.5 years old. More than 50% of the patients in both groups had underlying comorbidities such as diabetes mellitus, hypertension, and dyslipidemia. Three oncogenic miRNAs (miR-182, miR-301a, and miR-373) with high expression in the HCC tissues were selected as the candidate miRNAs. The expression level of serum exosomal mir-182, miR-301a, and miR-373 were significantly upregulated with fold change (fc) of 1.77, 2.52, and 1.67 (p< 0.05) respectively in NASH-induced liver cirrhosis with HCC as compared to the control group. The same trend could be observed in the expression level of ascitic fluid exosomal mir-182, miR-301a, and miR-373 whereby they were significantly upregulated with fc of 1.6, 1.94 and 2.13 (p <0.05) respectively in NASH-induced liver cirrhosis with HCC as compared to the control group. However, poor correlation of miRNA expression (miR-182, miR-301a and miR-373) between serum exosomal and ascitic fluid exosomal in HCC group with miR-182 (r=0.213, p=0.444), miR-301a (r= -0.242, p=0.422) and miR-373 (r=0.24, p=0.427). Conclusions A significant increase in the expression levels of exosomal miR-182, miR-301a, and miR-373 for both serum and ascitic fluid may be potential biomarkers for NASH-induced liver cirrhosis with HCC