ArticleClinical and molecular hepatology2025
Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway.
Article in Clinical and molecular hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed.
- Distinct Alpha-Fetoprotein Trajectories Preceding Hepatocellular Carcinoma Diagnosis: A Latent Class Mixed-Model Analysis.Cancers · 2026Article
- Review
- Correspondence to letter to the editor on "Distinct tumor immune microenvironment modulation by anti-PD-1/PD-L1, VEGF, and CTLA-4 blockade provides a rationale for triplet therapy in hepatocellular carcinoma".Clinical and molecular hepatology · 2026Article
- Unveiling the Intricate Dance: Signaling Pathways in Liver Cancer Metabolism and Immunity.Current oncology reports · 2026Review
- Correspondence to letter to the editor on "Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway".Clinical and molecular hepatology · 2026Article
- Critical flaws in the molecular classification of HCC based on metabolic zonation: Letter to the editor on "Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway".Clinical and molecular hepatology · 2026Article
- Clinical applications of immunogenomics in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Review
- Molecular classification and construction of prognostic risk model via machine learning based on metabolic-related genes in hepatocellular carcinoma.Translational cancer research · 2026Article
- Clinical Prediction of Glycolysis-Driven Molecular Subclass of Hepatocellular Carcinoma without Transcriptomic Profiling.Liver cancer · 2026Article
- CCT2 Orchestrates Glycolysis and Exosome-Mediated M2 Macrophage Polarization in HCC tumorigenesis.International journal of biological sciences · 2026Article
- TNFAIP1 suppresses hepatocellular carcinoma progression via the PXR/CYP3A4 signaling axis.American journal of cancer research · 2026Article
- Correspondence to editorial on "Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway".Clinical and molecular hepatology · 2026Article
- Molecular stratification of hepatocellular carcinoma by metabolic-signaling pathways guides precision immunotherapy and TACE therapy.Clinical and molecular hepatology · 2026Article
- Reply to correspondence on "Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway".Clinical and molecular hepatology · 2026Article
- Zonation, Zonation, Zonation: The Real Estate of the Liver.Annual review of pathology · 2026Review
- A novel link between tumor cell metabolism and patient prognosis: Editorial on "Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway".Clinical and molecular hepatology · 2026Article
- Single-cell RNA sequencing and spatial transcriptomic analysis reveal a distinct population of G6PDFrontiers in immunology · 2026Article
- Article
- Overexpression of S100 Calcium-Binding Protein A2 is Associated With Poor Prognosis in Hepatocellular Carcinoma.Cancer control : journal of the Moffitt Cancer CenterArticle
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
21 authors.
Funding
Abstract
BACKGROUND/
aimsPreviously, we advocated the importance of classifying hepatocellular carcinoma (HCC) based on physiological functions. This study aims to classify HCC by focusing on liver-intrinsic metabolism and glycolytic pathway in cancer cells.
methodsComprehensive RNA/DNA sequencing, immunohistochemistry, and radiological evaluations were performed on HCC tissues from the training cohort (n=136) and validated in 916 public samples. HCC was classified using hierarchical clustering and compared with previous molecular, histopathological, and hemodynamic classifications.
resultsLiver-specific metabolism and glycolysis are mutually exclusive and were divided into two major subclasses: The "rich metabolism" subclass (60.3%) is characterized by enhanced bile acid and fatty acid metabolism, wellto-moderate differentiation, microtrabecular or pseudoglandular pattern, and homogeneous arterial-phase hyperenhancement (APHE), corresponding to Hoshida S3 with favorable prognosis. In IL6-JAK-STAT3-high (25.0%) conditions, upregulated ALB expression, enhanced gluconeogenesis and urea cycle activity, and an inflammatorymicroenvironment are observed. Conversely, the Wnt/β-catenin-high environment (19.9%) features elevated GLUL, APOB and CYP3A4 expression, frequent CTNNB1 (D32-S37) mutations, and an immune-desert/excluded phenotype. The "glycolysis" subclass (39.7%), characterized by histopathological dedifferentiation and downregulated liver-specific metabolism, encompasses subclasses with PI3K/mTOR (20.6%) and NOTCH/TGF-β (19.1%) signaling. These often exhibit TP53 mutations, macrotrabecular massive or compact patterns, inhomogeneous/rim-APHE, and high expression of hypoxia-inducible factors and glucose transporters, corresponding to Hoshida S1/2 with poor prognosis.
conclusionThe loss of liver-specific metabolism correlates with morphological dedifferentiation, indicating cellular dedifferentiation may exhibit both physiological and pathological duality. Key signaling pathways involved in the maturation process from fetal to adult liver and zonation program may play a critical role in defining HCC diversity.
Indexed as
Identifiers
What OpenQuestion holds
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.