Negative Correlation Between ADC Values and GPC3 Expression in Hepatocellular Carcinoma: A Quantitative Diffusion-Weighted Imaging Study

Abstract

Objective To investigate the association between apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging (DWI) and glypican-3 (GPC3) expression in hepatocellular carcinoma (HCC), and to explore the potential of ADC as a non-invasive imaging biomarker for assessing GPC3 expression Methods This retrospective study included 468 patients with pathologically confirmed HCC who underwent preoperative liver magnetic resonance imaging between January 2020 and December 2025. Based on immunohistochemical staining, patients were classified into three groups: GPC3-negative (GPC3−, n=69), low-expression (GPC3+, n=42), and high-expression (GPC3++, n=357). Tumor ADC values, adjacent liver tissue ADC values, and tumor-to-liver ADC ratios were measured and compared among groups. Statistical analyses included the Kruskal–Wallis test, Mann–Whitney U-test with Bonferroni correction, and Spearman correlation analysis. Results Tumor ADC values differed significantly among the three groups (p<0.001), with median ADC values of 1.40 (1.34–1.46), 1.35 (1.28–1.42), and 1.27 (1.23–1.31) ×10−3 mm2/s in the GPC3−, GPC3+, and GPC3++ groups, respectively. The tumor-to-liver ADC ratios were 0.97 (0.94–1.00), 0.91 (0.88–0.94), and 0.87 (0.84–0.90), respectively, and also showed significant differences among groups (p<0.001). ADC values and ADC ratios were negatively correlated with GPC3 expression levels (r=−0.52 and r=−0.56, respectively; both p<0.001). Conclusion Higher GPC3 expression in HCC was associated with lower tumor ADC values. Quantitative DWI-derived ADC, including both tumor ADC and the tumor-to-liver ADC ratio, may serve as a promising imaging biomarker associated with GPC3 expression, potentially offering supportive information for preoperative evaluation of HCC.