Liquid biopsy in patients with hepatocellular carcinoma: Circulating tumor cells and cell-free nucleic acids

Abstract

Hepatocellular carcinoma (HCC), with its high incidence and mortality rate, is one of the most common malignant tumors. Despite recent development of a diagnostic and treatment method, the prognosis of HCC remains poor. Therefore, to provide optimal treatment for each patient with HCC, more precise and effective biomarkers are urgently needed which could facilitate a more detailed individualized decision-making during HCC treatment, including the following; risk assessment, early cancer detection, prediction of treatment or prognostic outcome. In the blood of cancer patients, accumulating evidence about circulating tumor cells and cell-free nucleic acids has suggested their potent clinical utilities as novel biomarker. This concept, so-called “liquid biopsy” is widely known as an alternative approach to cancer tissue biopsy. This method might facilitate a more sensitive diagnosis and better decision-making by obtaining genetic and epigenetic aberrations that are closely associated with cancer initiation and progression. In this article, we review recent developments based on the available literature on both circulating tumor cells and cell-free nucleic acids in cancer patients, especially focusing on Hepatocellular carcinoma.

Novel Liquid Biopsy Test Based on a Sensitive Methylated SEPT9 Assay for Diagnosing Hepatocellular Carcinoma

“…ctDNA is one of the targets in liquid biopsies and carries information on tumor‐specific genetic or epigenetic alterations. DNA methylation is one of these epigenetic alterations, and several studies have investigated ctDNA methylation in various genes . In this study, we focused on SEPT9 methylation.…”

“…Methylated ctDNA is among the most intensively investigated liquid biopsy targets. Because methylation changes in ctDNA occur early in carcinogenesis, numerous studies have evaluated the diagnostic performance of methylated genes, including cyclin‐dependent kinase inhibitor 2A ( CDKN2A ), Ras association domain family 1 isoform A ( RASSF1A ), and glutathione S‐transferase pi 1 ( GSTP1 ), in patients with HCC . However, the clinical usefulness of these methylated ctDNA tests in HCC remains limited.…”

Performance of different biomarkers for the management of hepatocellular carcinoma

“…Several studies have analysed the role of CTCs as a marker to predict survival, recurrence or treatment response in different kinds of tumors [53,57,58] . The presence of CTCs was reported for the first time in 1869 into the blood of a man with metastatic cancer [59] .…”

“…. Numerous studies have shown the potential utility of circulating cancer byproducts detection from which we could extract molecular information about primary tumors [51][52][53][54] . The liquid biopsy could be conducted in repeated samples providing accessible, accurate and dynamic information to evaluate the tumor status.…”

“…The liquid biopsy could be conducted in repeated samples providing accessible, accurate and dynamic information to evaluate the tumor status. These novel biomarkers are thought to have great potential and could provide individualized decision-making during HCC treatment, including the follow-up period; risk assessment, early cancer detection, treatment response or even prognostic outcome [53][54][55][56] .…”