Detection of macrotrabecular-massive hepatocellular carcinoma based on viscoelastic characteristics obtained by multifrequency magnetic-resonance elastography.

[OBJECTIVES] To investigate the use of viscoelastic characteristics obtained with magnetic-resonance elastography (MRE) in identifying the macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC) and its association with gene expression profiles.

[MATERIALS AND METHODS] Fifty-one patients (mean age, 56.2 ± 12.6 years; 42 men) with histologically proven HCCs (16 with the MTM subtype, and 35 without) and 47 healthy participants (mean age, 54.1 ± 13.7 years, 24 men) underwent preoperative MRI and MRE examinations and were prospectively enrolled. Tumor viscoelasticity (comprising c and φ), imaging features and clinical information were analyzed and diagnostic models developed. Logistic regression and area-under-the-curve (AUC) methodology evaluated the models' efficacy for determining the MTM-HCC. RNA sequencing and KEGG pathway analyses identified differential gene expression between 12 high-c and 12 low-c tumor samples.

[RESULTS] In HCC patients with elevated Edmondson-Steiner grades, satellite nodules, non-smooth margins, fat deficiency, or an arterial phase hypovascular component (APHC) more than 20%, tumor viscoelastic values c or φ were higher, compared with patients without these features (p < 0.05). Tumor c (T-c) was an independent predictor of MTM-HCC (AUC, 0.818; 95% confidence interval: 0.685, 0.950; p < 0.001); Combining T-c with ≥ 20% APHC yielded a higher AUC (0.843), but not significantly different from T-c alone (p = 0.533). RNA sequencing showed high-c tumors upregulated cell proliferation and DNA replication genes but downregulated immune regulation genes.

[CONCLUSION] MRE-derived T-c is a promising non-invasive biomarker for identifying MTM-HCC. HCCs with different T-c levels show distinct gene expression profiles, particularly in proliferation and immune pathways. Research with larger cohorts is needed to validate clinical utility.

[KEY POINTS] Question Can MRE-based viscoelastic values identify the macrotrabecular-massive (MTM) subtype of HCC? Findings Tumor-c based on MRE has a unique diagnostic performance for identifying MTM-HCC; tumor stiffness correlates with proliferative and immune gene expression. Clinical relevance MRE-based stiffness is a noninvasive predictor of MTM-HCC, and high-stiffness tumors show upregulation of proliferation genes and downregulation of immune genes. These findings may guide personalized treatment, but larger studies are required to confirm clinical applicability.