BioFact-MoE: Biologically Factorized Mixture of Experts for Vision-Language Prognostic Modeling in Hepatocellular Carcinoma

Multimodal survival prediction, a crucial yet challenging task, demands the integration of multimodal medical data (\eg Whole Slide Images (WSIs) and Genomic Profiles) to achieve accurate prognostic modeling. Given the inherent heterogeneity across modalities, the feature decoupling-fusion paradigm has emerged as a dominant approach. However, these methods have the following shortcomings: (1) fail to reduce the redundant information of modality features before decoupling, which negatively affects the feature decoupling and fusion effect;(2) lack the ability to model the fine-grained relationships of the features and capture the local information interactions between intra- and inter-modality features. To address these issues, we propose a \underline{H}ierarchical \underline{D}ecoupling-Fusion \underline{M}ixture-\underline{o}f-\underline{E}xperts (HDMoE) framework with two levels of MoE and \underline{R}andom \underline{F}eature \underline{R}eorganization (RFR) modules.In the first-level MoE, shared experts and routed experts are employed to remove redundant information and extract fine-grained specific features within each modality, while the second-level MoE facilitates fine-grained inter-modality feature decoupling. Besides, we design two RFR modules following each level of MoE to finely fuse intra- and inter-modality features, which can help the model capture more fine-grained relationships between modalities. Extensive experimental results on our private Liver Cancer (LC) and three TCGA public datasets confirm the effectiveness of our proposed method. Codes are available at https://github.com/ZJUMAI/HDMoE.

Hepatocellular carcinoma (HCC) is a common malignancy and a leading cause of cancer-related mortality. Current guidelines and staging systems provide coarse categories, but often miss within-stage heterogeneity and the clinical context in electronic medical records (EMRs). We present HCC-STAR (Hepatocellular Carcinoma Staging, Treatment And pRognosis), a clinically aligned large language model that reads routine EMR narratives and jointly outputs risk score-based staging, ranked guideline-consistent treatments with evidence-based rationales, and individualized survival estimates. We curated about 30,000 HCC cases from SEER and expanded them into EMR-style narrative training data using a clinician-validated, prompt-based augmentation workflow. On this corpus, we developed a knowledge-aligned reasoning framework optimized with a step-verifiable composite reward, moving beyond text-level memorization of clinical guidelines. In a multi-center cohort of 6,668 patients from 12 hospitals in China, HCC-STAR achieved state-of-the-art performance in treatment recommendation and risk stratification compared with clinical guidelines and competitive models, including GPT-5 and Gemini-2.5 Pro. Hypothetical overall-survival analysis showed a median survival of 51 months under adherence to HCC-STAR recommendations, compared with 29 and 32 months under BCLC and CNLC. In clinician-centric evaluations, blinded hepatobiliary specialists rated HCC-STAR's reasoning and evidence-based justifications as trustworthy. The model surpassed resident and attending physicians in treatment accuracy and helped physicians make more accurate decisions faster when used as an assistant. These findings support HCC-STAR as a reliable and verifiable decision-support system for risk stratification and precision therapy in HCC.

This study explores the use of deep learning and explainable artificial intelligence to diagnose hepatocellular carcinoma (HCC) and define effective biomarkers across five different stages of disease development using a transcriptomic biomarker HCC dataset constructed via semi-supervised learning from three source datasets. Several deep learning experiments were conducted with different feature extraction techniques and gene sets to identify the most effective features for training high-accuracy models with minimal loss. The best-performing model, using 15 selected genes with the SelectKBest algorithm, achieved 90.74% accuracy, while the model with the lowest recorded loss of 0.3187 was obtained using 20 selected genes. To address the issue of class imbalance in the dataset, a weighted training approach was conducted, and for model transparency and interpretability a SHAP-based XAI analysis provided insights into the model's decision-making, consistently finding DNAJB14 as the most influential gene. Functional validation in this study has provided compelling evidence that DNAJB14 plays an important role in the adverse properties of HCC and that its inhibition effectively reverses tumour cell migration, invasion, colony and sphere formation. The main limitation of this study is the dataset's class imbalance, and while weighted training helped mitigate this, further research and additional data are needed to guarantee model generalizability. Future studies should also explore the influence of genetic variations, environmental factors, and clinical differences on model performance across diverse populations.