ArticleCancers2021
Key Enzymes in Pyrimidine Synthesis, CAD and CPS1, Predict Prognosis in Hepatocellular Carcinoma.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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.
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Who cites it
36 citing papers in PubMed, 46 citations in OpenAlex.
- A Pan-Cancer Multi-Omics Analysis of CAD: Integrating CRISPR and Metabolomics Data to Unravel the Metabolic-Immune Axis and Immunotherapy Response.Biomedicines · 2026Article
- Conformational Dynamics of the Active Site Loop in Dihydroorotase Highlighting the Limitations of Loop-In Structures for Inhibitor Docking.International journal of molecular sciences · 2025Article
- ASS1 inhibits liver cancer by promoting CAD ubiquitination and reversing the urea cycle and pyrimidine synthesis imbalance.Hepatology communications · 2025Article
- Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion.Cell communication and signaling : CCS · 2025Review
- LM2I leads to CAD ubiquitination and liver cancer suppression through activation of ASS1.Acta biochimica et biophysica Sinica · 2025Article
- Increased Sirtuin 6 Activity in Tumor Cells Can Prompt CD4-Positive T-Cell Differentiation Into Regulatory T Cells and Impede Immune Surveillance in the Microenvironment.World journal of oncology · 2025Article
- Prognostic and Immunotherapeutic Predictive Value of CAD Gene in Hepatocellular Carcinoma: Integrated Bioinformatics and Experimental Analysis.Molecular biotechnology · 2025Article
- Erianin inhibits the proliferation of lung cancer cells by suppressing mTOR activation and disrupting pyrimidine metabolism.Cancer biology & medicine · 2025Article
- The Loop-In Binding Mode of Dihydroorotase: Implications for Ligand Binding and Therapeutic Targeting.International journal of molecular sciences · 2025Review
- Discovery of novel serum peptide biomarkers for cholangiocarcinoma recurrence through MALDI-TOF MS and LC-MS/MS peptidome analysis.Scientific reports · 2025Article
- Integrated analysis reveals an aspartate metabolism-related gene signature for predicting the overall survival in patients with hepatocellular carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- CHIP promotes CAD ubiquitination and degradation to suppress the proliferation and colony formation of glioblastoma cells.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- From the Inside Out: Exposing the Roles of Urea Cycle Enzymes in Tumors and Their Micro and Macro Environments.Cold Spring Harbor perspectives in medicine · 2024Review
- Construction and validation of a prognostic model for stemness-related genes in lung adenocarcinoma.Translational cancer research · 2024Article
- The emerging roles of glutamine amidotransferases in metabolism and immune defense.Nucleosides, nucleotides & nucleic acids · 2024Review
- Review
- Hypoosmosis alters hepatocyte mitochondrial morphology and induces selective release of carbamoyl phosphate synthetase 1.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Reduced Lipid Peroxidation Predicts Unfavorable Prognosis in Hepatocellular Carcinoma, but Not Intrahepatic Cholangiocarcinoma.Biomedicines · 2023Article
- M7G methylated core genes (METTL1 and WDR4) and associated RNA risk signatures are associated with prognosis and immune escape in HCC.BMC medical genomics · 2023Article
- p53 inhibits the Urea cycle and represses polyamine biosynthesis in glioma cell lines.Metabolic brain disease · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Patients with hepatocellular carcinoma (HCC) have a highly variable clinical course. Therefore, there is an urgent need to identify new prognostic markers to determine prognosis and select specific therapies. Recently, it has been demonstrated that dysregulation of the urea cycle (UC) is a common phenomenon in multiple types of cancer. Upon UC dysregulation, nitrogen is diverted toward the multifunctional enzyme carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD), and increases pyrimidine synthesis. In this study, we investigated the role of CAD and carbamoyl-phosphate synthetase 1 (CPS1), a rate-limiting enzyme of the UC highly expressed in hepatocytes, in HCC. We created a tissue microarray to analyze expression of both enzymes by immunohistochemistry in a large and well-characterized overall cohort of 871 HCCs of 561 patients that underwent surgery. CAD was induced in recurrent HCCs, and high expression predicted shorter overall survival. CPS1 was downregulated in HCC and further reduced in recurrent tumors and distant metastases. Additionally, low CPS1 was associated with short overall survival. A combined score of both enzymes was an independent prognostic marker in a multivariate Cox regression model (HR = 1.37, 95% confidence interval 1.06-1.75,
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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.