Serum-Exosome-Derived miRNAs Serve as Promising Biomarkers for 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.

Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study

“…Of these three miRNAs, only let-7a-5p is supported by multiple studies indicating that let-7a-5p can modulate cell growth, migration and invasion, cell proliferation and apoptosis, and importantly, that it is associated with hepatis B and viral carcinogenesis, as indicated in Figure 4 [60][61][62][63][64]. In a Chinese cohort where 74.8% of patients were HBV positive, three serum-exosome-derived miRNAs (miR-122-5p, let-7d-5p and miR-425-5p) with an AUC of 0.905 were identified as promising biomarkers for identifying HCC patients [225]. In a study in India, let-7a was also listed as a key potential biomarker in a sample where 27% of cases were HBV positive and 24% were HCV positive [226].…”

PIWI-interacting RNAs (PiRNAs) as emerging biomarkers and therapeutic targets in biliary tract cancers: A comprehensive review

“… Diagnostic Capacity piRNA Expression Mechanism Model Cell line Potential clinical utility Ref Hepatocellular carcinoma piR-Hep1 Up Enhances the survival, mobility, and infiltrative abilities of cells. Human, in vitro HKCI-4, HKCI-8 Prognostic marker [ 151 ] piR-1029, piR-15254 Up – Human – Diagnostic marker [ 242 ] piR-651 Up – In vitro HepG2 Diagnostic marker [ 207 ] Colorectal cancer Gastric cancer piR-1245 Up Augments cellular proliferation, movement, and infiltration while preventing programmed cell death through the interaction with specific mRNA molecules located within nuclear exosomes. Human, in vitro HCT116, SW480 Prognostic marker [ 144 ] piR-823 Up Encourages cellular multiplication and inhibits programmed cell death through the activation of HSF1 phosphorylation.…”

Exosomes: Diagnostic and Therapeutic Implications in Cancer

“…Increased levels of exosomes might represent a hallmark of malignant cancers, and they could serve as an indicator of clinical status [ 89 ]. Serum exosome-derived miRNAs (miR-122-5p, let-7d-5p, and miR-425-5p) can distinguish HCC patients from healthy donors [ 90 ]. The expression levels of exosomal miR-21, miR-155, miR-182, and miR-373 in the serum of breast cancer patients are higher than those in healthy controls [ 91 ].…”