Imaging-based surrogate markers of transcriptome subclasses and signatures in hepatocellular carcinoma: preliminary results
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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.
• 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.
KeywordsHepatocellular carcinoma Genomics Magnetic resonance imaging Computed tomography Biomarkers
American joint committee on cancer
Barcelona clinic liver cancer
Health insurance portability and accountability
Portal venous phase
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.
Written informed consent was waived by the Institutional Review Board.
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.
• performed at one institution
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