Reduced tumor stiffness quantified by tomoelastography as a predicative marker for glypican-3-positive hepatocellular carcinoma

BACKGROUND: Glypican-3 (GPC3) expression is investigated as a promising target for tumor-specific immunotherapy of hepatocellular carcinoma (HCC). This study aims to determine whether GPC3 alters the viscoelastic properties of HCC and whether tomoelastography, a multifrequency magnetic resonance elastography (MRE) technique, is sensitive to it. METHODS: Ninety-five participants (mean age, 58 ± 1 years; 78 men and 17 women) with 100 pathologically confirmed HCC lesions were enrolled in this prospective study from July 2020 to August 2021. All patients underwent preoperative multiparametric MRI and tomoelastography. Tomoelastography provided shear wave speed (c, m/s) representing tissue stiffness and loss angle (φ, rad) relating to viscosity. Clinical, laboratory, and imaging parameters were compared between GPC3-positive and -negative groups. Univariable and multivariable logistic regression were performed to determine factors associated with GPC3-positive HCC. The diagnostic performance of combined biomarkers was established using logistic regression analysis. Area-under-the-curve (AUC) analysis was done to assess diagnostic performance in detecting GPC3-positive HCC. FINDINGS: GPC3-positive HCCs (n=72) had reduced stiffness compared with GPC3-negative HCCs (n=23) while viscosity was not different (c: 2.34 ± 0.62 versus 2.72 ± 0.62 m/s, P=0.010, φ: 1.11 ± 0.21 vs 1.18 ± 0.27 rad, P=0.21). Logistic regression showed c and elevated serum alpha-fetoprotein (AFP) level above 20 ng/mL were independent factors for GPC3-positive HCC. Stiffness with a cutoff of c = 2.8 m/s in conjunction with an elevated AFP yielded a sensitivity of 80.3%, specificity of 70.8%, and AUC of 0.80. INTERPRETATION: Reduced stiffness quantified by tomoelastography may be a mechanical signature of GPC3-positive HCC. Combining reduced tumor stiffness and elevated AFP level may provide potentially valuable biomarker for GPC3-targeted immunotherapy.