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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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