ArticleJournal of hepatocellular carcinoma2025
Construction of 3D Enhanced CT Radiomics-Based Model to Predict Circadian Gene Expression and Prognosis in Hepatocellular Carcinoma.
Article in Journal of hepatocellular carcinoma, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Circadian disruption contributes to hepatocellular carcinoma (HCC) progression. This study aimed to develop a CT-based radiomics model to non-invasively predict circadian rhythm (CR) gene expression profiles for improved prognostic assessment. Methods: Mendelian randomization (MR) analysis revealed a significant causal association between CR disorders and the risk of HCC. In Cohort 1 (TCGA database, n = 424), 32 CR-related genes were identified from an initial set of 71 genes. Univariate Cox regression analysis identified 18 prognosis-related genes, and a risk model containing 8 genes was constructed using LASSO and multivariate Cox regression. This model was then validated in Cohort 2 (ICGC database, n = 232). The gene CRTC2 was further validated in vitro. Radiomics features were constructed based on enhanced CT images from Cohort 3 (TCIA database, n = 45) to predict CR risk genes, and the prognostic value of the model was validated in Cohort 4 (The Fourth Affiliated Hospital of Zhejiang University School of Medicine, n = 38). Results: The CR risk gene model stratified patients into high- and low-risk groups with significantly different survival outcomes in both TCGA and ICGC cohorts (TCGA: P < 0.001; ICGC: P = 0.029). The risk score was independently associated with overall survival (HR = 3.582, 95% CI: 2.101-6.107, P < 0.001). Experimental results confirmed that knockdown of CRTC2 significantly inhibited HCC cell proliferation, migration, invasion, and induced apoptosis. The radiomics model achieved an AUC of 0.931 in the training set and 0.760 in the validation set for predicting CR gene expression. Importantly, in the clinical validation cohort, patients with low radiomics scores had significantly longer survival (P = 0.039). Conclusion: Circadian rhythm-related gene expression, implicated in HCC development, can be non-invasively predicted via CT-based radiomics. The proposed model offers promise for prognostic stratification and personalized treatment planning in HCC.
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