Pathobiological Dictionary Defining Pathomics and Texture Features: Addressing Understandable AI Issues in Personalized Liver Cancer; Dictionary Version LCP1.0

Abstract: AI holds strong potential for medical diagnostics, yet its clinical adoption is limited by a lack of interpretability and generalizability. This study introduces the Pathobiological Dictionary for Liver Cancer (LCP1.0), a practical framework designed to translate complex Pathomics and Radiomics Features (PF and RF) into clinically meaningful insights aligned with existing diagnostic workflows. QuPath and PyRadiomics, standardized according to IBSI guidelines, were used to extract 333 imaging features from hepatocellular carcinoma (HCC) tissue samples, including 240 PF-based-cell detection/intensity, 74 RF-based texture, and 19 RF-based first-order features. Expert-defined ROIs from the public dataset excluded artifact-prone areas, and features were aggregated at the case level. Their relevance to the WHO grading system was assessed using multiple classifiers linked with feature selectors. The resulting dictionary was validated by 8 experts in oncology and pathology. In collaboration with 10 domain experts, we developed a Pathobiological dictionary of imaging features such as PFs and RF. In our study, the Variable Threshold feature selection algorithm combined with the SVM model achieved the highest accuracy (0.80, P-value less than 0.05), selecting 20 key features, primarily clinical and pathomics traits such as Centroid, Cell Nucleus, and Cytoplasmic characteristics. These features, particularly nuclear and cytoplasmic, were strongly associated with tumor grading and prognosis, reflecting atypia indicators like pleomorphism, hyperchromasia, and cellular orientation.The LCP1.0 provides a clinically validated bridge between AI outputs and expert interpretation, enhancing model transparency and usability. Aligning AI-derived features with clinical semantics supports the development of interpretable, trustworthy diagnostic tools for liver cancer pathology.