Serum-Exosome-Derived miRNAs Serve as Promising Biomarkers for HCC Diagnosis

SIMPLE SUMMARY: We aim to discover the ideal biomarkers for diagnosing HCC, by detecting the small RNAs (sRNAs) from serum exosomes. After analyzing the proportion and distribution of sRNAs species from serum exosomes, we found that miRNAs were the most important components in serum exosomes. Three serum-exosome-derived miRNAs (miR-122-5p, let-7d-5p, and miR-425-5p) had significant values for diagnosing HCC, both in the training set and validation set. Our results concluded that serum-exosome-derived miRNAs could be the promising biomarkers in HCC diagnosis ABSTRACT: Background: Serum exosomes are emerging as key liquid biopsy biomarkers for the early diagnosis of cancer. However, the proportion and distribution of small RNA (sRNA) species from serum exosomes of hepatocellular carcinoma (HCC) patients remain unclear. Effective and reliable biomarkers for HCC diagnosis should be explored. Methods: In this study, we aimed to use sRNA sequencing to profile the sRNAs of serum exosomes in HCC and non-tumor donors. The serum exosomes of 124 HCC patients and 46 non-tumor donors were enrolled for detecting the values of the potential biomarkers for the diagnosis of HCC. Results: We found that miRNAs accounted for the maximal percentage of all types of sRNAs both in the serum exosomes of HCC patients and non-tumor donors. This indicated that the serum-exosome-derived microRNAs (miRNAs) were the most valuable as potential biomarkers in HCC diagnosis. Then, miRNAs were set as research candidates. In our Chinese cohorts, three serum-exosome-derived miRNAs (miR-122-5p, let-7d-5p, and miR-425-5p) could be promising biomarkers for distinguishing HCC patients from non-tumor donors. In addition, they were preferred for the early diagnosis of HCC. We also presented the base distribution of some novel serum-exosome-derived miRNAs and described the potential values as biomarkers. Conclusions: The results suggested that the serum-exosome-derived miRNAs were the most crucial sRNA species and they highlighted the potential of serum-exosome-derived miRNAs as promising biomarkers for HCC diagnosis.