Tumour Markers for Hepatocellular Carcinoma

Enzymes and isoenzymes

  • Des-γ-carboxyprothrombin (DCP) and γ-glutamyl transferase (GGT) is expressed in larger HCC tumors, the sensitivity of being weaker compared with AFP when HCC was <3 cm in diameter, while it was stronger compared with AFP when HCC was >5 cm in diameter DCP is more accurately than AFP and AFP-L3.

The combined detection of DCP and AFP can predict the recurrence of HCC within 6 months after surgery

  • γ-glutamyl transferase (GGT) with DCP and AFP can significantly improve the rate of diagnosis of HCC. The sensitivity of GGT to detect small HCC is only 43.8%.
  • α-l-fucosidase (AFU) does not correlate with tumor size or the level of AFP. However,AFU can reveal the case 6–9 months earlier than ultrasonographic visualization. Combination of AFP and AFU can improve the sensitivity, specificity and diagnostic accuracy of AFP from 70, 85 and 79.7%, respectively, to 95, 100 and 99.1%, respectively.

Cytokines

  • Transforming growth factor-β1 (TGF-β1) and TGF-β1 mRNA may be used as sensitive indicators to diagnose HCC
  • VEGF is higher in HCC patients and overexpression is a biologic marker of tumor invasiveness and poor prognosis

Genetic biomarkers

  • AFP mRNA is the most valuable marker for circulating HCC cells. In advanced liver cancer, the rate of AFP mRNA expression reaches 100%. Moreover, the value of AFP mRNA serves as a predictor for HCC recurrence after surgery.
  • MicroRNA MiR-500 is a potential candidate biomarker for HCC along with promising biomarker of HCC.

MicroRNAs miR-29 and MiR-122 are downregulated in HCC cells indicating their role as a prognostic marker for HCC therapy.

Plasma miR-21 level in patients revealed sensitivity and specificity to be 87.3 and 92%, and can also be considered as a promising biomarker of HCC

  • Related genes including Δ-like 1 homolog (DLK1) in HCC is significantly elevated suggesting that DLK1 as an independent prognostic marker.

Hepatoma-associated gene (HTA) has recently been shown to be HCC tumor-specific and might play a key role in the early diagnosis and treatment of HCC.

Similarly, villin1 (Vil1) is another newly identified marker for HCC and can indicate poor differentiation, vascular invasion, advanced cancer stage and recurrence-free survival for high serum AFP-associated HCC.

Although a large body of data is available for following up a case of hepato-cellular carcinoma with its various proteomic and genomic tumour markers, there are no international guidelines to assist medical professionals make a systematic approach to diagnose and follow HCC patients without CT or MRI tests.

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