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

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 desg-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.

Circulating-Free DNA Analysis in Hepatocellular Carcinoma: A Promising Strategy to Improve Patients’ Management and Therapy Outcomes

“…DNA methylation is essential for normal development, playing an important role in key processes and, if dysregulated, it contributes to diseases such as cancer. The methylation of specific gene promoter is a well-known mechanism for transcriptional repression [47] which results in gene silencing [48]. On this basis, it emerges that aberrant methylation in a cancer-related gene promoter represents a tumor-specific event firstly associated to tumorigenesis [49].…”

“…Hypermethylation and hypomethylation typically occur in the CpG islands of the gene promoter region and, due to specific gene inactivation, had been involved in the development and progression of cancer through different processes [50]. Consequently, the detection of alteration in the DNA methylation could be potentially useful for the prediction, diagnosis and prognosis of patients with HCC [47]. The methylation pattern analysis includes some advantages over somatic mutation detection such as higher sensitivity, a dynamic range and the presence of a large amount of target regions.…”

LncRNAs in HCV Infection and HCV-Related Liver Disease

“…Like MALAT1, other lncRNAs are emerging as promising circulating biomarkers for diagnosis, prognosis, and response to therapy in cancer [142]. Current diagnostic and follow-up strategies for HCC rely heavily on medical image examination and AFP (alpha-fetoprotein) serum levels.…”

“…Although lncRNAs have already been studied as biomarkers in HCC (reviewed in [142]), only a handful have shown biomarker potential for HCV-HCC ( Figure 3, Table 2). One of them is UCA1.…”

Circulating Cell Free DNA and DNA Integrity Index as Discriminating Tools between Breast Cancer and Benign Breast Disease

“…Liquid biopsy means detection of nucleic acids originating from different body cells in biological samples as blood, saliva, urine or stool. In case of cancer; circulating tumor cells, circulating cellfree tumor DNA (ccf DNA), microvesicles containing mRNAs, micro RNAs (miRNAs) and proteins, could be measured in peripheral blood or other body fluids using specific techniques (Guerriero et al, 2019).…”