Abstract
Background
Nuclear β-catenin accumulation reflects activation of the Wnt/β-catenin pathway in hepatocellular carcinoma (HCC), but noninvasive preoperative prediction of this immunohistochemical phenotype remains incompletely established.Purpose
To develop and externally validate CT radiomics and topology-based intratumoral heterogeneity (ITH) models for preoperative prediction of nuclear β-catenin expression in HCC.Materials and methods
This multicenter retrospective study included 1029 patients with histopathologically confirmed HCC. Patients from two participating institutions formed the development cohort and were split into training (n=620; nuclear β-catenin-positive, 293) and internal validation (n=267; nuclear β-catenin-positive, 126) sets. Patients from an independent third institution formed the external validation cohort (n=142; nuclear β-catenin-positive, 43). Whole-tumor portal venous phase CT radiomics features and topology-based ITH features were extracted from the audited image-mask cohort. Model discrimination, calibration, and clinical utility were evaluated using AUC, bootstrap 95% confidence intervals, calibration summaries, Brier scores, and decision curve analysis.Results
In external validation, AUCs were 0.677 for the clinical model, 0.862 for the radiomics model, 0.857 for the ITH model, 0.831 for the core ITH model, 0.863 for the radiomics-ITH model, and 0.886 for the stacking model. Compared with radiomics alone, stacking showed a numerical ΔAUC of 0.024 (95% CI, -0.010 to 0.060; P=0.180).Conclusion
CT radiomics and topology-based ITH features showed external predictive value for nuclear β-catenin expression in HCC. The stacking model had the highest external AUC, but its improvement over radiomics alone was not statistically significant. If prospectively validated, these CT-based approaches could complement tissue assessment for pretreatment biological stratification.