ArticleCell death & disease2018
Dihydropyrimidine dehydrogenase predicts survival and response to interferon-α in hepatocellular carcinoma.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Dihydropyrimidine dehydrogenase modulates immune response to checkpoint inhibition in mismatch repair deficient/microsatellite instability-high colorectal cancer.Journal for immunotherapy of cancer · 2026Article
- Article
- Exploration and Validation of Pancreatic Cancer Hub Genes Based on Weighted Gene Co-Expression Network Analysis and Immune Infiltration Score Analysis.Pharmacogenomics and personalized medicine · 2023Article
- Modulation of the p38 MAPK Pathway by Anisomycin Promotes Ferroptosis of Hepatocellular Carcinoma through Phosphorylation of H3S10.Oxidative medicine and cellular longevity · 2022Article
- Deoxythymidylate Kinase as a Promising Marker for Predicting Prognosis and Immune Cell Infiltration of Pan-cancer.Frontiers in molecular biosciences · 2022Article
- Dihydropyrimidine dehydrogenase (DPYD) gene c.1627A>G A/G and G/G genotypes are risk factors for lymph node metastasis and distant metastasis of colorectal cancer.Journal of clinical laboratory analysis · 2021Article
- RNA sequencing analysis reveals the competing endogenous RNAs interplay in resected hepatocellular carcinoma patients who received interferon-alpha therapy.Cancer cell international · 2021Article
- DPYD, down-regulated by the potentially chemopreventive agent luteolin, interacts with STAT3 in pancreatic cancer.Carcinogenesis · 2021Article
- Epithelial-Mesenchymal Transition and MicroRNAs in Colorectal Cancer Chemoresistance to FOLFOX.Pharmaceutics · 2021Review
- Metabolic rewiring in the promotion of cancer metastasis: mechanisms and therapeutic implications.Oncogene · 2020Review
- Review
- A non-proliferative role of pyrimidine metabolism in cancer.Molecular metabolism · 2020Review
- Large-Scale TransgenicGenetics · 2020Article
- Triclosan treatment decreased the antitumor effect of sorafenib on hepatocellular carcinoma cells.OncoTargets and therapy · 2018Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis and recurrence contribute to poor prognosis of hepatocellular carcinoma (HCC). Recently, we reported that interferon-α (IFN-α) can suppress metastasis of HCC; however, the underlying mechanism has not been fully described. In this study, we demonstrated that expression of dihydropyrimidine dehydrogenase (DPYD), a pyrimidine catabolic enzyme, was dose-dependently downregulated by IFN-α in HCC tissues from nude mice. Notably, DPYD expression was found to be significantly increased in HCC cell lines with higher metastatic potentials compared with their controls. Moreover, upregulation of DPYD in HCC cells could promote in vitro migration, invasion, and in vivo lung metastasis, and inducing changes characteristic of epithelial-mesenchymal transition (EMT). In contrast, knockdown of DPYD inhibited these processes. Mechanistically, DPYD functioned as a positive regulator of EMT in HCC by targeting the p38/NF-κB/Snail1 pathway. Clinically, tissue microarray analysis showed that high DPYD expression was positively associated with aggressive tumor characteristics, including larger tumor size, tumor recurrence, and advanced tumor node metastasis (TNM) stage, and independently correlated with poorer overall survival times after curative resection. HCC patients with low DPYD expression have better response to IFN-α therapy. Taken together, our findings elucidate that IFN-α could downregulate DPYD expression to inhibit EMT and HCC metastasis, and suggest that DPYD might be a potential prognostic biomarker and a therapeutic target for HCC.
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