ArticleHepatology communications2022
Impact of Nuclear Factor Erythroid 2-Related Factor 2 in Hepatocellular Carcinoma: Cancer Metabolism and Immune Status.
Article in Hepatology communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Nuclear factor erythroid 2-related factor: potential use as a therapeutic strategy for viral infections.Archives of microbiology · 2026Review
- Silibinin Anticancer Effects Through the Modulation of the Tumor Immune Microenvironment in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- The Impact of TP53-Induced Glycolysis and Apoptosis Regulator on Prognosis in Hepatocellular Carcinoma: Association with Tumor Microenvironment and Ferroptosis.Liver cancer · 2025Article
- Ferroptosis: insight into the treatment of hepatocellular carcinoma.Cancer cell international · 2024Review
- Breaking the Barriers of Therapy Resistance: Harnessing Ferroptosis for Effective Hepatocellular Carcinoma Therapy.Journal of hepatocellular carcinoma · 2024Review
- Determinants of the maximal functional reserve during repeated supramaximal exercise by humans: The roles of Nrf2/Keap1, antioxidant proteins, muscle phenotype and oxygenation.Redox biology · 2023Article
- Clinical Significance of Signal Regulatory Protein Alpha (SIRPα) Expression in Hepatocellular Carcinoma.Annals of surgical oncology · 2023Article
- Antioxidants-related nuclear factor erythroid 2-related factor 2 gene variants associated with HBV-related liver disease.Cancer cell international · 2023Article
- Cancer-associated fibroblasts promote tumor cell growth via miR-493-5p in intrahepatic cholangiocarcinoma.Cancer science · 2023Article
- Ferroptosis is induced by lenvatinib through fibroblast growth factor receptor-4 inhibition in hepatocellular carcinoma.Cancer science · 2022Article
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We examined phosphorylated nuclear factor erythroid 2-related factor 2 (P-NRF2) expression in surgically resected primary hepatocellular carcinoma (HCC) and investigated the association of P-NRF2 expression with clinicopathological features and patient outcome. We also evaluated the relationship among NRF2, cancer metabolism, and programmed death ligand 1 (PD-L1) expression. In this retrospective study, immunohistochemical staining of P-NRF2 was performed on the samples of 335 patients who underwent hepatic resection for HCC. Tomography/computed tomography using fluorine-18 fluorodeoxyglucose was performed, and HCC cell lines after NRF2 knockdown were analyzed by array. We also analyzed the expression of PD-L1 after hypoxia inducible factor 1α (HIF1A) knockdown in NRF2-overexpressing HCC cell lines. Samples from 121 patients (36.1%) were positive for P-NRF2. Positive P-NRF2 expression was significantly associated with high alpha-fetoprotein (AFP) expression, a high rate of poor differentiation, and microscopic intrahepatic metastasis. In addition, positive P-NRF2 expression was an independent predictor for recurrence-free survival and overall survival. NRF2 regulated glucose transporter 1, hexokinase 2, pyruvate kinase isoenzymes L/R, and phosphoglycerate kinase 1 expression and was related to the maximum standardized uptake value. PD-L1 protein expression levels were increased through hypoxia-inducible factor 1α after NRF2 overexpression in HCC cells. Conclusions: Our large cohort study revealed that P-NRF2 expression in cancer cells was associated with clinical outcome in HCC. Additionally, we found that NRF2 was located upstream of cancer metabolism and tumor immunity.
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