ArticleBMC cancer2016
Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer.
Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 17 citations in OpenAlex.
- Fraternal cooperation of hierarchical cancer parallels metazoan multicellularity and eusociality.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Association of the expression of 5-FU biomarkers with aging and prognosis in elderly patients with lung cancer treated with S-1 adjuvant chemotherapy: Follow-up results of the Setouchi Lung Cancer Group Study 1201.Molecular and clinical oncology · 2025Article
- The effect of epidermal growth factor receptor mutation on adjuvant chemotherapy with tegafur/uracil for patients with completely resected, non-lymph node metastatic non-small cell lung cancer (> 2 cm): a multicenter, retrospective, observational study as exploratory analysis of the CSPOR-LC03 study.Japanese journal of clinical oncology · 2024Observational
- Effect of Tegafur-Uracil in Resected Stage IB Lung Adenocarcinoma According to Presence or Absence of Epidermal Growth Factor Receptor Gene Mutation: A Retrospective Cohort Study.Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia · 2024Article
- Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study.Current oncology (Toronto, Ont.) · 2024Article
- Anti-EGF antibodies as surrogate biomarkers of clinical efficacy in stage IIIB/IV non-small-cell lung cancer patients treated with an optimized CIMAvax-EGF vaccination schedule.Oncoimmunology · 2020Article
- A case-control study to assess the ability of the thymine challenge test to predict patients with severe to life threatening fluoropyrimidine-induced gastrointestinal toxicity.British journal of clinical pharmacology · 2020Article
- Thymidine phosphorylase affects clinical outcome following surgery and mRNA expression levels of four key enzymes for 5-fluorouracil metabolism in patients with stage I and II non-small cell lung cancer.Molecular and clinical oncology · 2018Article
- Retracted Article: FOXC1 silencing promotes A549 cell apoptosis through inhibiting the PI3K/AKT/hedgehog/Gli2 signaling pathway.RSC advances · 2018Article
- The role of HGF-MET pathway and CCDC66 cirRNA expression in EGFR resistance and epithelial-to-mesenchymal transition of lung adenocarcinoma cells.Journal of hematology & oncology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIt has been shown that epidermal growth factor receptor (EGFR) mutation status is associated with 5-fluorouracil (5-FU) sensitivity in non-small-cell lung cancer (NSCLC). However, the relationship between EGFR mutation status and dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, is unknown.
methodsWe elucidated the crosstalk among the EGFR signal cascade, the DPD gene (DPYD), and DPD protein expression via the transcription factor Sp1 and the effect of EGFR mutation status on the crosstalk.
resultsIn the PC9 (exon19 E746-A750) study, EGF treatment induced up-regulation of both Sp1 and DPD; gefitinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI), and mithramycin A, a specific Sp-1 inhibitor, suppressed them. Among EGFR-mutated (PC9, HCC827; exon19 E746-A750 and H1975; exon21 L858R, T790M, gefitinib resistant) and -non-mutated (H1437, H1299) cell lines, EGF administration increased DPYD mRNA expression only in mutated cells (p < 0.05). Accordingly, gefitinib inhibited DPD protein expression only in PC9 and HCC827 cells, and mithramycin A inhibited it in EGFR-mutated cell lines, but not in wild-type. FU treatment decreased the level of cell viability more in gefitinib-treated EGFR-TKI sensitive cell lines. Further, combination treatment of FU and mithramycin A suppressed cell viability even in a gefitinib resistant cell line.
conclusionsThe EGFR signal cascade regulates DPD expression via Sp1 in EGFR mutant cells. These results might be a step towards new therapies targeting Sp1 and DPD in NSCLC with different EGFR mutant status.
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.