ArticleJournal of hepatology2014
Sequential transcriptome analysis of human liver cancer indicates late stage acquisition of malignant traits.
Article in Journal of hepatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 93 citations in OpenAlex.
- Integration of histopathology and molecular features for the classification of benign and malignant hepatocellular neoplasms.Virchows Archiv : an international journal of pathology · 2026Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Common Signaling Pathways in Cancer and Alzheimer's Disease May Point to New Treatments.Current topics in medicinal chemistry · 2025Review
- Endocrine and cellular physiology and pathology of the insulin-like growth factor acid-labile subunit.Nature reviews. Endocrinology · 2024Review
- Dynamics of Wnt/β-catenin reporter activity throughout whole life in a naturally short-lived vertebrate.npj aging · 2024Article
- Harnessing function of EMT in cancer drug resistance: a metastasis regulator determines chemotherapy response.Cancer metastasis reviews · 2024Review
- Review
- Advances in Histological and Molecular Classification of Hepatocellular Carcinoma.Biomedicines · 2023Review
- HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis.International journal of molecular sciences · 2023Review
- Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise.World journal of hepatology · 2023Review
- Wnt signaling in liver regeneration, disease, and cancer.Clinical and molecular hepatology · 2023Review
- Prognosis-Related Molecular Subtypes and Immune Features Associated with Hepatocellular Carcinoma.Cancers · 2022Article
- Sequential gene expression analysis of cervical malignant transformation identifies RFC4 as a novel diagnostic and prognostic biomarker.BMC medicine · 2022Article
- Benign liver tumours: understanding molecular physiology to adapt clinical management.Nature reviews. Gastroenterology & hepatology · 2022Review
- Current and Emerging Molecular Markers of Liver Diseases: A Pathogenic Perspective.Gene expression · 2022Article
- [Up-to-date Knowledge on the Pathological Diagnosis of Hepatocellular Carcinoma].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2021Review
- WNT as a Driver and Dependency in Cancer.Cancer discovery · 2021Review
- Epigenetic modifications precede molecular alterations and drive human hepatocarcinogenesis.JCI insight · 2021Article
- Article
- Mutations and mechanisms of WNT pathway tumour suppressors in cancer.Nature reviews. Cancer · 2021Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsHuman hepatocarcinogenesis is as a multi-step process starting from dysplastic lesions to early carcinomas (eHCC) that ultimately progress to HCC (pHCC). However, the sequential molecular alterations driving malignant transformation of the pre-neoplastic lesions are not clearly defined. This lack of information represents a major challenge in the clinical management of patients at risk.
methodsWe applied next-generation transcriptome sequencing to tumor-free surrounding liver (n = 7), low- (n = 4) and high-grade (n = 9) dysplastic lesions, eHCC (n = 5) and pHCC (n = 3) from 8 HCC patients with hepatitis B infection. Integrative analyses of genetic and transcriptomic changes were performed to characterize the genomic alterations during hepatocarcinogenesis.
resultsWe report that changes in transcriptomes of early lesions including eHCC were modest and surprisingly homogenous. Extensive genetic alterations and subsequent activation of prognostic adverse signaling pathways occurred only late during hepatocarcinogenesis and were centered on TGFβ, WNT, NOTCH, and EMT-related genes highlighting the molecular diversity of pHCC. We further identify IGFALS as a key genetic determinant preferentially down-regulated in pHCC.
conclusionsOur results define new hallmarks in molecular stratification and therapy options for patients at risk for HCC, and merit larger prospective investigations to develop a modified clinical-decision making algorithm based on the individualized next-generation sequencing analyses.
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Registered trials
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.