ArticleNature communications2024
Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Mosaic Accumulation of Somatic Genetic Variation and Estimates of Age in the Long-Lived Reef-Building Coral Acropora palmata.Molecular ecology · 2026Article
- IGFBP3 As a Potential Biomarker and Therapeutic Target in Hepatocellular Carcinoma: A Multi-Cohort Analysis.Journal of clinical laboratory analysis · 2026Article
- Integrated genomic analyses identify oncogenic pathway interplay in hepatocarcinogenesis defining specific molecular subtypes.Nature communications · 2026Article
- Selective sweep probabilities in spatially expanding populations.Nature communications · 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
- The Heterogeneity and Function of Stromal Cells in the Tumor Microenvironment.Research (Washington, D.C.) · 2026Review
- Decoding the spatial logic of immune evasion in hepatocellular carcinoma: from single-cell profiling to spatial omics.Frontiers in immunology · 2026Review
- Spatial Transcriptomics and snRNA-seq Expose CAF Niches Orchestrating Dual Stromal-Immune Barriers in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.Signal transduction and targeted therapy · 2025Review
- Beyond the ratio of tumor reduction: residual volume after induction chemotherapy emerges as the optimal biomarker in advanced nasopharyngeal cancer.Radiation oncology (London, England) · 2025Article
- Detecting branching rate heterogeneity with tree balance statistics in lineage tracing trees.bioRxiv : the preprint server for biology · 2025Article
- Integrative Spatial Transcriptomics and Experimental Validation Reveal UBC-Mediated EMT Associated with Immune Evasion in Hepatocellular Carcinoma.ImmunoTargets and therapy · 2025Article
- The Prognostic Value of Peripheral Blood Inflammatory Markers in Hepatocellular Carcinoma Treated with Lenvatinib Combined with PD-1 Inhibitors.Journal of hepatocellular carcinoma · 2025Article
- Single-cell and spatial omics unravel the spatiotemporal biology of tumour border invasion and haematogenous metastasis.Clinical and translational medicine · 2024Review
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16 authors.
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Abstract
Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a "spatially competing distribution" (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.
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