ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2019
Genomic and transcriptional heterogeneity of multifocal hepatocellular carcinoma.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 122 citations in OpenAlex.
- Single-cell immune signature for detecting early-stage HCC and early assessing anti-PD-1 immunotherapy efficacy.Journal for immunotherapy of cancer · 2022Trial
- Tumour Mutation Burden Does Not Predict Immune Cell Frequency or Risk of Recurrence After Surgery in Hepatocellular Carcinoma.Cancers · 2026Article
- Deep learning-assisted tumor radiomic dynamics on MRI predict pathological complete response in HCC undergoing immune-based therapy followed by hepatectomy.Hepatology (Baltimore, Md.) · 2026Article
- Hepatocellular carcinoma metastasis-immune microenvironment crosstalk: emerging mechanisms and immunotherapy.Cellular & molecular biology letters · 2026Review
- Successful treatment of β-catenin-positive, immune checkpoint inhibitor-resistant tumor in a case of multicentric hepatocellular carcinoma.Clinical journal of gastroenterology · 2026Article
- How the gut microbiome affects the immunotherapy response in hepatocellular carcinoma.Cancer biology & medicine · 2026Review
- Multi-omics profiling reveals divergent biology and liver microenvironment in HCC of metastatic and de novo origin.Molecular cancer · 2026Article
- The inflammatory state of tumor peripheral liver tissue affects hepatocellular carcinoma progression and prognosis.Discover oncology · 2026Article
- Prognostic outcomes of surgery vs. non-surgery in initially unresectable HCC with successful conversion via ICI + TKI therapy.BMC gastroenterology · 2026Article
- A novel pathologic scoring system for predicting postoperative recurrence in BCLC stage 0-A hepatocellular carcinoma patients: a nationwide multicenter study.Science China. Life sciences · 2026Article
- Network Pharmacology and Molecular Docking Identify Medicarpin as a Potent CASP3 and ESR1 Binder Driving Apoptotic and Hormone-Dependent Anticancer Activity.International journal of molecular sciences · 2025Article
- Immune infiltration landscape and potential drug-targeted implications for hepatocellular carcinoma with 'progression/hyper-progression' recurrence.Annals of medicine · 2025Article
- Prognostic modeling and immune infiltration analysis in hepatocellular carcinoma using glutathione metabolism-associated genes.European journal of medical research · 2025Article
- Intrahepatic Microbial Heterogeneity in Multifocal Hepatocellular Carcinoma and Its Association with Host Genomic and Transcriptomic Alterations.Cancer discovery · 2025Article
- Decoding Genomic Diversity to Guide Tumor Lesion-Specific Treatment of Multifocal Hepatocellular Carcinoma.Cancer medicine · 2025Article
- Unraveling the immune-activated tumor microenvironment correlated with clinical response to atezolizumab plus bevacizumab in advanced HCC.JHEP reports : innovation in hepatology · 2025Article
- Increases in 4-Acetaminobutyric Acid Generated by Phosphomevalonate Kinase Suppress CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A novel MYC-ZNF706-SLC7A11 regulatory circuit contributes to cancer progression and redox balance in human hepatocellular carcinoma.Cell death and differentiation · 2024Article
- Combination of bulk RNA and single-cell sequencing unveils PANoptosis-related immunological ecology hallmarks and classification for clinical decision-making in hepatocellular carcinoma.Scientific reports · 2024Article
- HOXA9 promotes proliferation, metastasis and prevents apoptosis in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2024Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) often presents with multiple nodules within the liver, with limited effective interventions. The high genetic heterogeneity of HCC might be the major cause of treatment failure. We aimed to characterize genomic heterogeneity, infer clonal evolution, investigate RNA expression pattern and explore tumour immune microenvironment profile of multifocal HCC. PATIENTS AND
methodsWhole-exome sequencing and RNA sequencing were carried out in 34 tumours and 6 adjacent normal liver tissue samples from 6 multifocal HCC patients. Protein expression of Ki67, AFP, P53, Survivin and CD8 was detected by immunohistochemistry. Fluorescence in situ hybridization was carried out to validate the amplification status of sorafenib-targeted genes.
resultsWe deciphered genomic and transcriptional heterogeneity among tumours in each multifocal HCC patient including mutational profiles, copy number alterations, tumour evolutionary trajectory and tumour immune microenvironment profiles. Of note, sorafenib-targeted alterations were identified in the trunk of phylogenetic tree in only one out of the six patients, which may explain the relative low treatment response rate to sorafenib in clinical practice. Moreover, we demonstrated RNA expression patterns and tumour immune microenvironment profiles of all nodules. We found that RNA expression pattern was associated with Edmondson-Steiner grading. Based on the differential expression of 66 reported immune markers, unsupervised hierarchical clustering analysis of 34 nodules identified immune subsets: one low expression cluster with seven nodules and one high expression cluster with 11 nodules. CD8+ T cells were more enriched in nodules of the high expression cluster.
conclusionsOur study provided a detailed view of genomic and transcriptional heterogeneity, clonal evolution and immune infiltration of multifocal HCC. The heterogeneity of druggable targets and immune landscape might help interpret the clinical responsiveness to targeted drugs and immunotherapy for multifocal HCC patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.