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 <Emphasis Type="BoldItalic">Question</Emphasis> Can MRE-based viscoelastic values identify the macrotrabecular-massive (MTM) subtype of HCC? <Emphasis Type="BoldItalic">Findings</Emphasis> Tumor-c based on MRE has a unique diagnostic performance for identifying MTM-HCC; tumor stiffness correlates with proliferative and immune gene expression. <Emphasis Type="BoldItalic">Clinical relevance</Emphasis> 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. Graphical Abstract

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

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2025年10月9日

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Zhen Wang,
Qi Liang,
Jia Luo,
Yunjie Liao,
Junhong Duan,
Qin Liu,
Qiyuan Chen,
Ze Mi,
Hongpei Tan,
Pengfei Rong

摘要

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.

Graphical Abstract