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

  • Hepatobiliary-Pancreas
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Abstract

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.

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Abbreviations

AJCC:

American joint committee on cancer

AP:

Arterial phase

BCLC:

Barcelona clinic liver cancer

CT:

Computed tomography

ER:

Enhancement ratio

HCC:

Hepatocellular carcinoma

HIPAA:

Health insurance portability and accountability

MR:

Magnetic resonance

PVP:

Portal venous phase

SI:

Signal intensity

WOR:

Washout ratio

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Author information

Authors and Affiliations

  1. Department of Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, Box 1234, New York, NY, 10029, USA

    Bachir Taouli & Shingo Kihira

  2. Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Bachir Taouli, Suguru Kakite & Mathilde Wagner

  3. Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Bachir Taouli, Yujin Hoshida, Xintong Chen, Poh Seng Tan, Xiaochen Sun, Kensuke Kojima, Sara Toffanin, Hadassa Hirschfield & Josep M. Llovet

  4. Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Yujin Hoshida, Xintong Chen, Poh Seng Tan, Xiaochen Sun, Kensuke Kojima, Sara Toffanin, Hadassa Hirschfield & Josep M. Llovet

  5. Division of Radiology, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, 36-1, Nishicho, Yonago City, 683-8504, Japan

    Suguru Kakite

  6. Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Health System, Singapore, Singapore

    Poh Seng Tan

  7. Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    M. Isabel Fiel

  8. UPMC, Department of Radiology, Hôpital Pitié-Salpêtrière, Sorbonne Universités, Assistance Publique-Hôpitaux de Paris, Paris, France

    Mathilde Wagner

  9. HCC Translational Research Laboratory, Barcelona-Clínic Liver Cancer Group Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Universitat de Barcelona (UB), Barcelona, Spain

    Josep M. Llovet

  10. Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain

    Josep M. Llovet

Authors
  1. Bachir Taouli
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  2. Yujin Hoshida
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  4. Xintong Chen
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  5. Poh Seng Tan
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  6. Xiaochen Sun
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  7. Shingo Kihira
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  8. Kensuke Kojima
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  9. Sara Toffanin
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  10. M. Isabel Fiel
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  12. Mathilde Wagner
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  13. Josep M. Llovet
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Corresponding author

Correspondence to Bachir Taouli.

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Guarantor

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.

Funding

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.

Methodology

• retrospective

• observational

• performed at one institution

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Taouli, B., Hoshida, Y., Kakite, S. et al. Imaging-based surrogate markers of transcriptome subclasses and signatures in hepatocellular carcinoma: preliminary results. Eur Radiol 27, 4472–4481 (2017). https://doi.org/10.1007/s00330-017-4844-6

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  • DOI: https://doi.org/10.1007/s00330-017-4844-6

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