Imaging-based surrogate markers of transcriptome subclasses and signatures in hepatocellular carcinoma: preliminary results

Eur Radiol. 2017 Nov;27(11):4472-4481. doi: 10.1007/s00330-017-4844-6. Epub 2017 Apr 24.


Objectives: In this preliminary study, we examined whether imaging-based phenotypes are associated with reported predictive gene signatures in hepatocellular carcinoma (HCC).

Methods: Thirty-eight patients (M/F 30/8, mean age 61 years) who underwent pre-operative CT or MR imaging before surgery as well as transcriptome profiling were included in this IRB-approved single-centre retrospective study. Eleven qualitative and four quantitative imaging traits (size, enhancement ratios, wash-out ratio, tumour-to-liver contrast ratios) were assessed by three observers and were correlated with 13 previously reported HCC gene signatures using logistic regression analysis.

Results: Thirty-nine HCC tumours (mean size 5.7 ± 3.2 cm) were assessed. Significant positive associations were observed between certain imaging traits and gene signatures of aggressive HCC phenotype (G3-Boyault, Proliferation-Chiang profiles, CK19-Villanueva, S1/S2-Hoshida) with odds ratios ranging from 4.44-12.73 (P <0.045). Infiltrative pattern at imaging was significantly associated with signatures of microvascular invasion and aggressive phenotype. Significant but weak associations were also observed between each enhancement ratio and tumour-to-liver contrast ratios and certain gene expression profiles.

Conclusions: This preliminary study demonstrates a correlation between phenotypic imaging traits with gene signatures of aggressive HCC, which warrants further prospective validation to establish imaging-based surrogate markers of molecular phenotypes in HCC.

Key points: • There are associations between imaging and gene signatures of aggressive hepatocellular carcinoma. • Infiltrative type is associated with gene signatures of microvascular invasion and aggressiveness. • Infiltrative type may be a surrogate marker of microvascular invasion gene signature.

Keywords: Biomarkers; Computed tomography; Genomics; Hepatocellular carcinoma; Magnetic resonance imaging.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Gene Expression Profiling / methods*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transcriptome*


  • Biomarkers