Abstract
Exosomal microRNAs (exo-miRs) have been promising cancer biomarkers. MiRs in hepatocellular carcinoma (HCC) cell-derived exosomes (HEX) were analyzed to identify reliable serum biomarkers for HCC. To detect overexpressed miRs in HEX, extracted exosomal small RNAs from human HCC cell lines and normal hepatocytes were sequenced and analyzed. Clinical significance of the overexpressed miRs in HEX was evaluated using quantitative real-time PCR (qRT-PCR) on serum samples of a validation cohort consisting of 28 healthy individuals, 60 with chronic liver disease, and 90 with HCC. We found 49 significantly overexpressed miRs in HEX compared to a normal hepatocyte. Among them, miR-10b-5p, miR-18a-5p, miR-215-5p, and miR-940 were overexpressed in HCC tissues and also associated with prognosis of HCC in the analysis of a public omics database. qRT-PCR analysis of the four serum exo-miRs in the validation cohort revealed serum exo-miR-10b-5p as a promising biomarker for early-stage HCC with 0.934 area under the curve (AUC) (sensitivity, 90.7%; specificity, 75.0%; cutoff value, 1.8-fold). Overexpression of serum exo-miR-215-5p was found to be significantly associated with poor disease-free survival in patients with HCC. Serum exo-miR-10b-5p is a potential biomarker for early-stage HCC, while serum exo-miR-215-5p can be used as prognostic biomarker for HCC.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and third leading cause of cancer-related mortality worldwide [1]
CD63-immunostained transmission electron microscope (TEM) revealed that all isolated samples consisted of CD63-positive spherical vesicles about 30–100 nm in size, which confirmed the efficiency of exosome isolation (Figure 1a)
49 exo-miRs were detected as predominantly overexpressed miRs in HCC cell-derived exosome (HEX) (>1.5-fold) compared to miR expression in THLE-2-derived exosomes (Figure 1c)
Summary
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and third leading cause of cancer-related mortality worldwide [1]. Though HCC is known as intractable cancer with poor prognosis, patients diagnosed at a very early stage (tumor size ≤2 cm) have a five-year survival rate of more than 70% after effective therapeutic treatment [2]. Abdominal ultrasound with or without serum alpha-fetoprotein (AFP) is used for HCC surveillance. While abdominal ultrasound is recommended in all guidelines, usage of serum AFP as a tumor biomarker remains controversial due to low sensitivity and suboptimal cost-effectiveness in the detection of early-stage HCC [3].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
