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Guerriero et al. Hepatoma Res 2019;5:6 Hepatoma Research
DOI: 10.20517/2394-5079.2018.108

Review Open Access

Circulating tumor DNAs and non-coding RNAs as
potential biomarkers for hepatocellular carcinoma
diagnosis, prognosis and response to therapy

Paola Guerriero , Farzaneh Moshiri , Laura Lupini , Silvia Sabbioni , Massimo Negrini , Elisa Callegari 1
1
2
1
1
3
1 Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara 44121, Italy.
2 Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran
11369, Iran.
3 Department of Life Sciences and Biotechnologies, University of Ferrara, Ferrara 44121, Italy.
Correspondence to: Dr. Massimo Negrini, Elisa Callegari, Department of Morphology, Surgery and Experimental Medicine, University of
Ferrara, Via Fossato di Mortara 70, Ferrara 44121, Italy. E-mail: ngm@unife.it, elisa.callegari@unife.it

How to cite this article: Guerriero P, Moshiri F, Lupini L, Sabbioni S, Negrini M, Callegari E. Circulating tumor DNAs and non-coding
RNAs as potential biomarkers for hepatocellular carcinoma diagnosis, prognosis and response to therapy. Hepatoma Res 2019;5:6.
http://dx.doi.org/10.20517/2394-5079.2018.108

Received: 20 Nov 2018 First Decision: 17 Dec 2018 Revised: 3 Jan 2019 Accepted: 4 Jan 2019 Published: 19 Feb 2019

Science Editor: Jin-Lin Hou Copy Editor: Cui Yu Production Editor: Huan-Liang Wu

Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide and despite
improvement in therapeutic approaches, prognosis remains poor. This can be partly attributed to the fact that the
majority of HCCs are diagnosed at intermediate or advanced stages. Availability of circulating biomarkers able
to detect HCC at early stages could improve patients’ prognosis. At present, however, alpha fetoprotein or des-
g-carboxyprothrombin are unable to reliably detect HCC at early stages and better circulating biomarkers are
needed. Circulating tumor DNA (ctDNA) and non-coding RNAs (ncRNAs) are emerging as promising biomarkers
to achieve the goal. Genetic and epigenetic alterations in ctDNA allow to pinpoint tumor-specific biomarkers,
reveal tumor heterogeneity, help monitor tumor evolution over time and assess therapy efficacy. It remains to
be fully evaluated the possibility of detecting these biomarkers at early tumor stages. Circulating ncRNAs are
quantitative biomarkers with potential use in diagnostic, prognostic and predictive clinical settings. They may
help to reveal HCC at early stages. However, because of heterogeneous and sometimes conflicting reported
results, they still require validation and standardization of pre-analytical and analytical approaches before clinical
applications could be envisaged.

Keywords: Liquid biopsy, hepatocellular carcinoma, circulating tumor DNA, non-coding RNA, diagnosis, prognosis,
therapy response

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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