ArticleClinical and molecular hepatology2026
Integrative multi-omics profiling identifies infiltrative hepatocellular carcinoma as an immunotherapy-resistant subtype with distinct molecular features.
Article in Clinical and molecular hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Molecular biomarkers for diagnosis, prognosis, precision therapy, and immunotherapy in cholangiocarcinoma, cHCC-CCA, and HCC.Hepatology communications · 2026Review
- Prediction of Response to Immunotherapy in Hepatocellular Carcinoma: Where Do We Stand?Cancers · 2026Review
- Regorafenib as Second-Line Versus Later-Line Therapy in Advanced Hepatocellular Carcinoma: A Multicenter Real-World Study with Exploratory Analysis of Prior Immune Checkpoint Inhibitor Exposure.Targeted oncology · 2026Article
- Article
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- Correspondence to letter to the editor on "Integrative multi-omics profiling identifies infiltrative hepatocellular carcinoma as an immunotherapy-resistant subtype with distinct molecular features".Clinical and molecular hepatology · 2026Article
- Infiltrative hepatocellular carcinoma resistance: Integrating microenvironment, host factors, and therapy.Clinical and molecular hepatology · 2026Article
- Efficacy of Nivolumab plus Ipilimumab in Advanced Hepatocellular Carcinoma with and without High-Risk Features: An International Multicenter Study.Liver cancer · 2026Article
- CAPTYN, a Blood-Based Machine-Learning Model Predicting Clinical Benefit of Atezolizumab-Bevacizumab in Hepatocellular Carcinoma: Validation in the IMbrave150 Trial.Cancer communications (London, England) · 2026Article
- Functional Interpretation of Recurrent Genetic Variants in Hepatocellular Carcinoma: Molecular Consequences and Clinical Relevance.Human mutation · 2026Review
- Prognostic Significance of Glypican-3 Expression in Hepatocellular Carcinoma Treated with Atezolizumab-Bevacizumab.Cancers · 2025Article
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26 authors.
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Abstract
BACKGROUND/
aimsHepatocellular carcinoma (HCC) exhibits substantial morphological and biological heterogeneity. Clinical and molecular relevance of the infiltrative subtype remains poorly defined in the context of cancer immunotherapy. We aimed to evaluate the prognostic impact and molecular features of infiltrative HCC in patients treated with first-line atezolizumab plus bevacizumab (Ate/Bev).
methodsWe included 307 patients with advanced HCC treated with Ate/Bev and classified them into four gross morphological types based on imaging. Multi-omics profiling was conducted on tumor samples. Type IV infiltrative signature was derived and externally validated using five independent HCC cohorts, including IMbrave150.
resultsInfiltrative morphology, encompassing pure and mixed forms, was present in 42.7% of advanced HCC and associated with advanced disease features and compromised liver function. Patients with type IV infiltrative HCC showed lowest objective response rate (14.6%) and worst progression-free (median, 2.8 months) and overall survival (median, 7.1 months). Infiltrative morphology remained an independent predictor of poor outcomes after multivariable adjustment for confounders, including intrahepatic tumor extent. Genomic profiling revealed enriched TP53 and ATM loss-of-function mutations in type IV infiltrative HCC. Transcriptomic and proteomic analyses identified consistent activation of tumor proliferation, epithelial-mesenchymal transition, TGF-β signaling, and immunosuppressive pathways in type IV infiltrative HCC. Type IV infiltrative signature was significantly associated with poor survival across external datasets and retained independent prognostic value.
conclusionsInfiltrative HCC is a clinically aggressive and molecularly distinct subtype of advanced HCC. Morphological classification and type IV infiltrative signatures may guide risk stratification and therapeutic decision-making in advanced HCC treated with immunotherapy.
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