Liquid biopsy derived circulating tumor cells and circulating tumor DNA as novel biomarkers in hepatocellular carcinoma

Expert Rev Mol Diagn. 2022 May;22(5):507-518. doi: 10.1080/14737159.2022.2094706. Epub 2022 Jun 29.


Introduction: The diagnosis of hepatocellular carcinoma (HCC) is made at a relatively advanced stage resulting in poor prognosis. Alpha-fetoprotein and liver ultrasound have limited accuracy as biomarkers in HCC. Liver biopsy provides information on tumor biology; however, it is invasive and holds high threat of tumor seeding. Thus, more accurate and less invasive approaches are needed.

Areas covered: Highly sensitive liquid biopsy assays have made possible the detection and analysis of cells or organelles such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and tumor-derived exosomes. Here, we focus on CTCs and ctDNA components of liquid biopsy and their clinical application as diagnostic, prognostic, and predictive biomarkers in HCC. Unlike tissue biopsy, liquid biopsy involves attaining a sample at several time frames in an easy and a non-invasive manner. They have been efficacious in detecting and classifying cancer, in predicting treatment response, in monitoring disease relapse and in identifying mechanisms of resistance to targeted therapies.

Expert opinion: Although interesting and highly promising, liquid biopsy techniques still have many obstacles to overcome before their wide spread clinical application sees the light. It is expected that these techniques will be incorporated into traditional methodologies for better diagnostic, predictive and prognostic results.

Keywords: Biomarker; CTC; clinical implication; ctDNA; hepatocellular carcinoma; liquid biopsy.

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Circulating Tumor DNA* / genetics
  • Humans
  • Liquid Biopsy / methods
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • Neoplastic Cells, Circulating* / pathology


  • Biomarkers, Tumor
  • Circulating Tumor DNA