Biomarkers for the early diagnosis of hepatocellular carcinoma

World J Gastroenterol. 2015 Oct 7;21(37):10573-83. doi: 10.3748/wjg.v21.i37.10573.


Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the 5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α-fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers, such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article, we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC.

Keywords: Biomarker; Des-γ-carboxyprothrombin; Glypican-3; Golgi protein-73; Hepatocellular carcinoma; MicroRNAs; Osteopontin; Squamous cell carcinoma antigen; α-fetoprotein; α-fetoprotein-L3.

Publication types

  • Review

MeSH terms

  • Annexin A2 / metabolism
  • Antigens, Neoplasm / metabolism
  • Biomarkers / metabolism
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / metabolism*
  • Early Detection of Cancer
  • Fibrosis / complications
  • Glypicans / metabolism
  • Humans
  • Inflammation / complications
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / metabolism*
  • Membrane Proteins / metabolism
  • MicroRNAs / metabolism
  • Midkine
  • Nerve Growth Factors / metabolism
  • Osteopontin / metabolism
  • Protein Precursors / metabolism
  • Prothrombin / metabolism
  • Receptors, Urokinase Plasminogen Activator / metabolism
  • Serpins / metabolism
  • Thioredoxins / metabolism
  • alpha-Fetoproteins / metabolism


  • Annexin A2
  • Antigens, Neoplasm
  • Biomarkers
  • Biomarkers, Tumor
  • GOLM1 protein, human
  • GPC3 protein, human
  • Glypicans
  • MDK protein, human
  • Membrane Proteins
  • MicroRNAs
  • Nerve Growth Factors
  • Protein Precursors
  • Receptors, Urokinase Plasminogen Activator
  • SPP1 protein, human
  • Serpins
  • alpha-Fetoproteins
  • squamous cell carcinoma-related antigen
  • Osteopontin
  • Midkine
  • Thioredoxins
  • acarboxyprothrombin
  • Prothrombin