ArticleNational science review2022
Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma: the PLANET study.
Article in National science review, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed.
- Asia-Pacific Transplant Oncology Symposium 2024: Expert Statements on the Current State and Future Direction of Hepatobiliary Surgical and Transplant Oncology.Liver cancer · 2026Review
- Spatial multi omic profiling maps hypoxia-driven pro-fibrotic SPP1Experimental hematology & oncology · 2026Article
- Spatially-guided metabolomics profiling of metabolic regions in human tumor tissues.Molecular systems biology · 2026Article
- Integrative genomic, transcriptomic, and metabolomic profiling of Dillenia suffruticosa.Scientific reports · 2026Article
- Multiomics and multi-region spatial transcriptome analysis reveal cellular networks and pathways associated with HCC recurrence.JHEP reports : innovation in hepatology · 2026Article
- Spatial transcriptomic-metabolic features of tumor foci and tumor capsule in microvascular invasion with hepatocellular carcinoma: A spatial multi-omics study.PLoS medicine · 2026Article
- Computational analysis of multi-omics data reveals CXCL10Cellular and molecular life sciences : CMLS · 2026Article
- Integrated multi-omics analysis reveals comprehensive metabolism-driven tumor heterogeneity and immune microenvironment in hepatocellular carcinomas.Scientific reports · 2026Article
- Full spatio-temporal analyses of migration and colonization in evolution-dense 3D mapping of cancer metastases provides new insights.Molecular biology and evolution · 2026Article
- Role of intratumoral heterogeneity in metastatic progression and drug resistance.Discover oncology · 2025Review
- The molecular characteristics of DNA damage and repair related to P53 mutation for predicting the recurrence and immunotherapy response in hepatocellular carcinoma.Scientific reports · 2025Article
- Article
- Spatial heterogeneity reveals an evolutionary signature predicting therapeutic response and clinical outcomes in hepatocellular carcinoma.Frontiers in bioinformatics · 2025Article
- Intra-tumor heterogeneity-resistant gene signature predicts prognosis and immune infiltration in breast cancer.Frontiers in immunology · 2025Article
- The theory of massively repeated evolution and full identifications of cancer-driving nucleotides (CDNs).eLife · 2024Article
- Characterization of cancer-driving nucleotides (CDNs) across genes, cancer types, and patients.eLife · 2024Article
- Single cell-spatial transcriptomics and bulk multi-omics analysis of heterogeneity and ecosystems in hepatocellular carcinoma.NPJ precision oncology · 2024Article
- Unveiling correlations between aristolochic acids and liver cancer: spatiotemporal heterogeneity phenomenon.Chinese medicine · 2024Review
- Development and validation of a novel immune‒metabolic-Based classifier for hepatocellular carcinoma.Heliyon · 2024Article
- GATA4 downregulation enhances CCL20-mediated immunosuppression in hepatocellular carcinoma.Hepatology communications · 2024Article
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Abstract
Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.
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