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

Abstract

Objectives In this preliminary study, we examined whether imaging-based phenotypes are associated with reported predictive gene signatures in hepatocellular carcinoma (HCC). Methods 38 patients (M/F 30/8, mean age 61 y) 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 4 quantitative imaging traits (size, enhancement ratios, wash-out ratio, tumour-to-liver contrast ratios) were assessed by 3 observers and were correlated with 13 previously reported HCC gene signatures by using logistic regression analysis. Results 39 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 of enhancement ratios 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.

Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases

“…There is also active development of novel cancer biomarker assays, including assays for cancer‐specific DNA mutations, differentially methylated regions of DNA, microRNAs, long noncoding RNAs, native and posttranslationally modified proteins, and biochemical metabolites. Recent results suggest that there is differential expression of many biomolecules in exosomes released from tumor cells compared to those from normal cells …”

MRI-based radiomics model for preoperative prediction of 5-year survival in patients with hepatocellular carcinoma

“…41 Some preliminary studies have revealed correlations between phenotypic imaging traits and genomic signatures in patients with HCC. 42,43 However, the small-sample size and limited imaging features may influence the reliability of the detected image-to-gene associations. Future studies could attempt to incorporate genomic characteristics into the radiomics model to capture more underlying behaviours in HCC.…”

Background, current role, and potential applications of radiogenomics

“…While similar to the prior study using CT, the pathologic identification of MVI may not correspond directly to a venous invasion genetic signature, and the results are not directly comparable. More recently, gene signatures of aggressive HCC phenotype were found to be associated with certain imaging traits in HCC imaged by contrast‐enhanced CT (26 patients) and MRI (12 patients), with an infiltrative pattern on imaging showing the highest number of positive associations . Interestingly, the authors did not find associations between enhancement ratios and gene expression signatures, but they propose the use of dynamic contrast‐enhanced (DCE)‐MRI for future prospective analyses given the limitation inherent to measurements of tumoral enhancement on arterial and portal venous phases alone.…”

“…More recently, gene signatures of aggressive HCC phenotype were found to be associated with certain imaging traits in HCC imaged by contrast-enhanced CT (26 patients) and MRI (12 patients), with an infiltrative pattern on imaging showing the highest number of positive associations. 39 Interestingly, the authors did not find associations between enhancement ratios and gene expression signatures, but they propose the use of dynamic contrast-enhanced (DCE)-MRI for future prospective analyses given the limitation inherent to measurements of tumoral enhancement on arterial and portal venous phases alone. Multiparametric MRI was later performed in a study of 14 patients with available HCC gene expression profiles at the same institution.…”