Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Circulating Extracellular Vesicle-Derived microRNAs as Novel Diagnostic and Prognostic Biomarkers for Non-Viral-Related Hepatocellular Carcinoma

Version 1 : Received: 17 August 2023 / Approved: 17 August 2023 / Online: 18 August 2023 (10:56:55 CEST)

A peer-reviewed article of this Preprint also exists.

Boonkaew, B.; Satthawiwat, N.; Pinjaroen, N.; Chuaypen, N.; Tangkijvanich, P. Circulating Extracellular Vesicle-Derived microRNAs as Novel Diagnostic and Prognostic Biomarkers for Non-Viral-Related Hepatocellular Carcinoma. Int. J. Mol. Sci. 2023, 24, 16043. Boonkaew, B.; Satthawiwat, N.; Pinjaroen, N.; Chuaypen, N.; Tangkijvanich, P. Circulating Extracellular Vesicle-Derived microRNAs as Novel Diagnostic and Prognostic Biomarkers for Non-Viral-Related Hepatocellular Carcinoma. Int. J. Mol. Sci. 2023, 24, 16043.

Abstract

Extracellular vesicle-derived microRNAs (EV-miRNAs) are promising circulating biomarkers for chronic liver disease. In this study, we explored the potential significance of plasma EV-miRNAs in non-hepatitis B-, non-hepatitis C-related HCC (NBNC-HCC). We compared plasma EV-miRNA profiles between NBNC-HCC and control groups including non-alcoholic fatty liver disease (NAFLD) and healthy controls using NanoString method. The differentially expressed EV-miRNAs were validated in another set of plasma samples by qRT-PCR. A total of 66 significantly differentially expressed EV-miRNAs between the HCC and control groups were identified in the discovery set. In the validation cohort including plasma samples of 70 NBNC-HCC, 70 NAFLD and 35 healthy controls, 5 plasma EV-miRNAs were significantly elevated in HCC, which included miR-19-3p, miR-16-5p, miR-223-3p, miR-30d-5p, and miR-451a. These miRNAs were found to participate in several cancer-related signaling pathways based on bioinformatic analysis. Among them, EV-miR-19-3p exhibited the best diagnostic performance and displayed a high sensitivity for detecting AFP-negative HCC and early-stage HCC. In multivariate analysis, high EV-miR-19-3p level was demonstrated as an independently unfavorable predictor of overall survival in patients with NBNC-HCC. In conclusion, our data have indicated for the first time that EV-miR-19-3p could serve as a novel circulating biomarker for the diagnosis and prognosis of NBNC-HCC.

Keywords

Extracellular vesicles; Nonalcoholic fatty liver disease; Hepatocellular carcinoma; microRNAs; Biomarker

Subject

Medicine and Pharmacology, Gastroenterology and Hepatology

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