ArticleEBioMedicine2019
Variants in oxidative stress-related genes affect the chemosensitivity through Nrf2-mediated signaling pathway in biliary tract cancer.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 30 citations in OpenAlex.
- Selenium-Related Genes Modulate Susceptibility to Parkinson's Disease Via Combination and SNCA-Interactive Effects Rather than Independent Effects: A Case-Control Study.Biological trace element research · 2026Article
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- The PIK3CA/AKT pathway drives therapy resistance in rhabdomyosarcoma.Nature communications · 2025Article
- Predictive value of immunomodulatory-related genes for the prognosis of lung adenocarcinoma based on bioinformatics analysis.Discover oncology · 2025Article
- Sleeve gastrectomy ameliorates renal injury in obesity-combined hyperuricemic nephropathy mice by modulating the AMPK/Nrf2/ABCG2 pathway.Scientific reports · 2024Article
- Natural medicinal compounds target signal transduction pathways to overcome ABC drug efflux transporter-mediated multidrug resistance in cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- Molecular aspects of ABCB1 and ABCG2 in Gallbladder cancer and its clinical relevance.Molecular and cellular biochemistry · 2023Article
- Association of variations in theFrontiers in pharmacology · 2023Article
- STING Suppresses Mitochondrial VDAC2 to Govern RCC Growth Independent of Innate Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Role of PPARG in Chemosensitivity-Regulating Network for Hypopharyngeal Squamous Cell Carcinoma.PPAR research · 2023Article
- ROS regulation in gliomas: implications for treatment strategies.Frontiers in immunology · 2023Review
- Article
- Oxidative Stress in Type 2 Diabetes: The Case for Future Pediatric Redoxomics Studies.Antioxidants (Basel, Switzerland) · 2022Review
- Multiple genetic variations of chronic rhinosinusitis with nasal polyps are associated with respiratory parameters in men with obstructive sleep apnea.Sleep & breathing = Schlaf & Atmung · 2022Article
- Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases.International journal of molecular sciences · 2021Article
- Proteomic analysis identifies deregulated metabolic and oxidative-associated proteins in Italian intrahepatic cholangiocarcinoma patients.BMC cancer · 2021Article
- The use of an oxidative stress scoring system in prognostic prediction for kidney renal clear cell carcinoma.Cancer communications (London, England) · 2021Article
- β-Elemene Enhances the Sensitivity of Osteosarcoma Cells to Doxorubicin via Downregulation of Peroxiredoxin-1.OncoTargets and therapy · 2021Article
- The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies.Antioxidants (Basel, Switzerland) · 2020Review
- NRF2: The key to tumor- and patient-dependent chemosensitivity in biliary tract cancer?EBioMedicine · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOxidative stress and their effectors play critical roles in carcinogenesis and chemoresistance. However, the role of oxidative stress-related genes variants in biliary tract cancer (BTC) chemoresistance remains unknown. In this work, we aim to investigate oxidative stress-dependent molecular mechanisms underlying chemoresistance, and find potential biomarkers to predict chemotherapy response for BTC.
methodsSixty-six SNPs in 21 oxidative stress-related genes were genotyped and analyzed in 367 BTC patients. Immunoblot, immunohistochemical, immunofluorescent, quantitative PCR, chromatin immunoprecipitation analysis and study of animal xenograft models were performed to discover oxidative stress-related susceptibility genes underlying chemoresistance mechanism of BTC.
findingsWe found that 3 functional polymorphisms (CAT_rs769217, GPX4_rs4807542, and GSR_rs3779647), which were shown to affect their respective gene expression levels, modified the effect of chemotherapy on overall survival (OS). We then demonstrated that knockdown of GPX4, CAT, or GSR induced chemoresistance through elevation of ROS level and activation of Nrf2-ABCG2 pathway in BTC cell lines. Moreover, the association between Nrf2 expression and BTC prognosis is only found in patients who received chemotherapy. Knockdown of Nrf2 enhanced chemosensitivity or even eliminated postoperative recurrence in BTC xenograft mouse models. Importantly, upon chemotherapy treatment patients harboring high oxidative stress-related score received higher survival benefit from adjuvant chemotherapy compared with patients with low oxidative stress-related score.
interpretationThe result of our study suggests, for the first time, that the oxidative stress-related score calculated by combining variations in CAT, GPX4, and GSR or Nrf2 expression could be used for predicting the chemosensitivity of BTC patients. FUND: This work was supported by the National Science Foundation of China, Foundation of Shanghai Shen Kang Hospital Development Center, and Shanghai Outstanding Academic Leaders Plan.
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.