The use of minimally invasive biomarkers for the diagnosis and prognosis of hepatocellular carcinoma

Biochim Biophys Acta Rev Cancer. 2020 Dec;1874(2):188451. doi: 10.1016/j.bbcan.2020.188451. Epub 2020 Oct 14.


Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide. Despite advances in systemic therapies, patient survival remains low due to late diagnosis and frequent underlying liver diseases. HCC diagnosis generally relies on imaging and liver tissue biopsy. Liver biopsy presents limitations because it is invasive, potentially risky for patients and it frequently misrepresents tumour heterogeneity. Recently, liquid biopsy has emerged as a way to monitor cancer progression in a non-invasive manner. Tumours shed content into the bloodstream, such as circulating tumour cells (CTCs), circulating nucleic acids, extracellular vesicles and proteins, that can be isolated from biological fluids of patients with HCC. These biomarkers provide knowledge regarding the genetic landscape of tumours and might be used for diagnostic or prognostic purposes. In this review, we summarize recent literature on circulating biomarkers for HCC, namely CTCs, circulating tumour DNA (ctDNA), RNA, extracellular vesicles and proteins, and their clinical relevance in HCC.

Keywords: Biomarker; Circulating tumor DNA (ctDNA); Circulating tumor cells (CTCs); Hepatocellular carcinoma; Liquid biopsy; Liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / genetics
  • Cell-Free Nucleic Acids / genetics
  • Disease Progression
  • Early Detection of Cancer
  • Extracellular Vesicles / genetics
  • Extracellular Vesicles / metabolism
  • Humans
  • Liquid Biopsy
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Neoplastic Cells, Circulating / metabolism
  • Prognosis


  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids