European Radiology

, Volume 27, Issue 11, pp 4472–4481 | Cite as

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

  • Bachir TaouliEmail author
  • Yujin Hoshida
  • Suguru Kakite
  • Xintong Chen
  • Poh Seng Tan
  • Xiaochen Sun
  • Shingo Kihira
  • Kensuke Kojima
  • Sara Toffanin
  • M. Isabel Fiel
  • Hadassa Hirschfield
  • Mathilde Wagner
  • Josep M. Llovet



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


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.


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.


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.


Hepatocellular carcinoma Genomics Magnetic resonance imaging Computed tomography Biomarkers 



American joint committee on cancer


Arterial phase


Barcelona clinic liver cancer


Computed tomography


Enhancement ratio


Hepatocellular carcinoma


Health insurance portability and accountability


Magnetic resonance


Portal venous phase


Signal intensity


Washout ratio


Compliance with ethical standards


The scientific guarantor of this publication is Bachir Taouli

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.


This study has received funding from

• National Institute of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK099558).

• NCI grant (1P30CA165979-01)

• European Commission Horizon 2020 (HEP-CAR, proposal 667273-2)

• the Samuel Waxman Cancer Research Foundation

• Grant I + D Program (SAF2013-41027)

• the Asociación Española Contra el Cáncer (AECC).

• Fondation ARC (SAE2014060 1302).XXX.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

All study subjects have been previously reported in: Chiang DY, Villanueva A, Hoshida Y, et al. Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Res. 2008;68(16):6779-88.


• retrospective

• observational

• performed at one institution

Supplementary material

330_2017_4844_MOESM1_ESM.docx (133 kb)
ESM 1 (DOCX 132 kb)


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Copyright information

© European Society of Radiology 2017

Authors and Affiliations

  • Bachir Taouli
    • 1
    • 2
    • 3
    Email author
  • Yujin Hoshida
    • 3
    • 4
  • Suguru Kakite
    • 2
    • 5
  • Xintong Chen
    • 3
    • 4
  • Poh Seng Tan
    • 3
    • 4
    • 6
  • Xiaochen Sun
    • 3
    • 4
  • Shingo Kihira
    • 1
  • Kensuke Kojima
    • 3
    • 4
  • Sara Toffanin
    • 3
    • 4
  • M. Isabel Fiel
    • 7
  • Hadassa Hirschfield
    • 3
    • 4
  • Mathilde Wagner
    • 2
    • 8
  • Josep M. Llovet
    • 3
    • 4
    • 9
    • 10
  1. 1.Department of RadiologyIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Translational and Molecular Imaging InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA
  3. 3.Liver Cancer Program, Tisch Cancer InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA
  4. 4.Division of Liver Diseases, Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkUSA
  5. 5.Division of Radiology, Department of Pathophysiological and Therapeutic Science, Faculty of MedicineTottori UniversityYonago CityJapan
  6. 6.Division of Gastroenterology and Hepatology, University Medicine ClusterNational University Health SystemSingaporeSingapore
  7. 7.Department of PathologyIcahn School of Medicine at Mount SinaiNew YorkUSA
  8. 8.UPMC, Department of Radiology, Hôpital Pitié-SalpêtrièreSorbonne UniversitésParisFrance
  9. 9.HCC Translational Research Laboratory, Barcelona-Clínic Liver Cancer Group Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de BarcelonaUniversitat de Barcelona (UB)BarcelonaSpain
  10. 10.Institució Catalana de Recerca i Estudis AvançatsBarcelonaSpain

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