ArticlePloS one2020
Serum copper, zinc and metallothionein serve as potential biomarkers for hepatocellular carcinoma.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 70 citations in OpenAlex.
- Harnessing copper-iron crosstalk: A novel strategy to combat hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- Zinc in Soil-Plant-Human Systems: A Synthesis of Its Fate, Essential Roles, and Health Implications.Scientifica · 2026Review
- The role of circulating metallothionein 1 in voriconazole-associated hepatotoxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Emerging Roles of Metallothioneins in Human Pathophysiology: A Review.Health science reports · 2025Article
- Tumor glucose reprogramming suppresses cuproptosis: A review.Biomolecules & biomedicine · 2025Review
- Responsive ROS-Augmented Prodrug Hybridization Nanoassemblies for Multidimensionally Synergitic Treatment of Hepatocellular Carcinoma in Cascade Assaults.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Differences in Tissue Copper and Zinc Content Between Normal Livers and Those with Cirrhosis with or Without Hepatocellular Carcinoma.International journal of molecular sciences · 2025Article
- Blood and Serum Copper and Zinc Levels and 10-Year Survival of Patients After Kidney Cancer Diagnosis.Nutrients · 2025Article
- Study of plasma essential element concentrations to explore markers of acute myocardial infarction.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- Metallothioneins in the Pathogenesis of Liver Diseases: A Review.International journal of hepatology · 2025Review
- Mechanisms of copper metabolism and cuproptosis: implications for liver diseases.Frontiers in immunology · 2025Review
- Predictive value of biomarkers for lenvatinib in hepatocellular carcinoma.Therapeutic advances in medical oncology · 2025Review
- Review
- Cuproptosis, the novel type of oxidation-induced cell death in thoracic cancers: can it enhance the success of immunotherapy?Cell communication and signaling : CCS · 2024Review
- Zinc Deficiency as a General Feature of Cancer: a Review of the Literature.Biological trace element research · 2024Review
- Chronic Aroclor 1260 exposure alters the mouse liver proteome, selenoproteins, and metals in steatotic liver disease.Environmental toxicology and pharmacology · 2024Article
- The Influence of Diet and Its Components on the Development and Prevention of Hepatocellular Carcinoma (HCC).Cancers · 2024Review
- Current Trends on the Involvement of Zinc, Copper, and Selenium in the Process of Hepatocarcinogenesis.Nutrients · 2024Review
- Micronutrients Importance in Cancer Prevention-Minerals.Cancer treatment and research · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCopper (Cu) and zinc (Zn) are essential nutrients and cofactors of enzymatic reactions with their binding partner. Metallothionein (MT) plays an important role in protecting against heavy metals and oxidative injury, however it may also portend drug resistance and a worse prognosis for hepatocellular carcinoma (HCC) patients. The aim of this study was to determine the amount of Cu, Zn, Cu/Zn and MT in evaluating a group of patients with HCC, including those treated with lenvatinib.
methodsWe enrolled 175 patients with HCC (139 men, 36 women; mean age 71.1 years; hepatitis C virus n = 85, hepatitis B virus n = 19, hepatitis C virus and hepatitis B virus n = 2, non-alcoholic steatohepatitis n = 39, alcohol n = 25, others n = 5; Child-Pugh A n = 141, Child-Pugh B n = 30, Child-Pugh C n = 4; Barcelona clinic liver cancer (BCLC) stage 0 n = 38, stage A n = 56, stage B n = 39, stage C n = 38, stage D n = 4). We evaluated the associations between Cu, Zn and MT. The study outcome was liver cancer-specific survival. Moreover, we treated 12 HCC patients with lenvatinib and investigated the changes in MT during lenvatinib therapy.
resultsThe serum level of Cu was positively correlated with alanine aminotransferase and the BCLC stage. The serum level of Zn decreased concordant with liver disease progression. Patients with a Cu/Zn ratio≥0.999 had significantly improved rates of survival when compared to patients with a Cu/Zn ratio<0.999 (45.3 vs. 30.1 months, p<0.001). MT was significantly correlated with the Cu/Zn ratio and increased after the administration of lenvatinib. Using multivariate Cox regression analyses, it was determined that the Cu/Zn ratio (hazard ratio [HR]: 1.442, p = 0.008), alpha-fetoprotein (HR: 1.000, p<0.001) and BCLC stage (HR: 2.087, p<0.001) were independent predictors of survival.
conclusionsThe Cu/Zn ratio could serve as a useful predictive marker for survival in cases of HCC. MT levels increased in HCC patients receiving lenvatinib therapy, and maybe a predictor of reduced survival.
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