ArticleBMC medical genomics2022
An asparagine metabolism-based classification reveals the metabolic and immune heterogeneity of hepatocellular carcinoma.
Article in BMC medical genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 19 citations in OpenAlex.
- Prognostic Genes Linked to Asparagine Metabolism in Hepatocellular Carcinoma: Identification, Validation, and Regulatory Mechanisms Based on Transcriptome and Single-Cell RNA Sequencing.International journal of molecular sciences · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Reprogramming Metabolism and Immunity: Nanotechnology's Promise for Hepatocellular Carcinoma Precision Therapy.International journal of nanomedicine · 2026Review
- Integrated multi-omics analysis of metabolomics and proteomics uncovers dysregulated amino acid metabolism in HCC metastasis.Frontiers in immunology · 2026Article
- Pan-cancer molecular signatures connecting aspartate transaminase to cancer prognosis, metabolic and immune signatures.Frontiers in oncology · 2026Article
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Distinct Metabolomic and Lipoprotein Signatures in Gall Bladder Cancer Patients of Black African Ancestry.Cancers · 2025Article
- Review
- Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway.Clinical and molecular hepatology · 2025Article
- The glycolytic characteristics of hepatocellular carcinoma and its interaction with the microenvironment: a comprehensive omics study.Journal of translational medicine · 2025Article
- IGF2BP1 accelerates the aerobic glycolysis to boost its immune escape in hepatocellular carcinoma microenvironment.Frontiers in immunology · 2024Article
- CD69 serves as a potential diagnostic and prognostic biomarker for hepatocellular carcinoma.Scientific reports · 2023Article
- Metabolic Reprogramming of HCC: A New Microenvironment for Immune Responses.International journal of molecular sciences · 2023Review
- A High-Throughput Sequencing Data-Based Classifier Reveals the Metabolic Heterogeneity of Hepatocellular Carcinoma.Cancers · 2023Article
- Influenced tumor microenvironment and tumor immunity by amino acids.Frontiers in immunology · 2023Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
INTRODUCTION AND
objectiveshepatocellular carcinoma (HCC) is the major form of liver cancer with a poor prognosis. Amino acid metabolism has been found to alter in cancers and contributes to malignant progression. However, the asparagine metabolism status and relevant mechanism in HCC were barely understood.
methodsBy conducting consensus clustering and the least absolute shrinkage and selection operator regression of HCC samples from three cohorts, we classified the HCC patients into two subtypes based on asparagine metabolism level. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analyses and Gene Set Enrichment Analysis of the differentially expressed genes between two subgroups were conducted. Immune cell infiltration was evaluated using CIBERSORT algorithm. The prognostic values of genes were analyzed by univariate and multivariate cox regression, ROC curve and Kaplan-Meier survival estimate analyses. Cell types of sing-cell RNA sequencing (scRNA-seq) data were clustered utilizing UMAP method.
resultsHCC patients with higher asparagine metabolism level have worse prognoses. Moreover, we found the distinct energy metabolism patterns, DNA damage response (DDR) pathway activating levels, drug sensitivities to DDR inhibitors, immune cell compositions in the tumor microenvironment and responses to immune therapy between two subgroups. Further, we identified a potential target gene, glutamic-oxaloacetic transaminase 2 (GOT2). GOT2 downregulation was associated with worse HCC prognosis and increased infiltration of T regulatory cells (Tregs). ScRNA-seq revealed the GOT2 downregulation in cancer stem cells compared with HCC cells.
conclusionsTaken together, HCC subtype which is more reliant on asparagine and glutamine metabolism has a worse prognosis, and a core gene of asparagine metabolism GOT2 is a potential prognostic marker and therapeutic target of HCC. Our study promotes the precision therapy of HCC and may improve patient outcomes.
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