ArticleBritish journal of cancer2019
High hepatic expression of PDK4 improves survival upon multimodal treatment of colorectal liver metastases.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Markers of liver regeneration-the role of growth factors and cytokines: a systematic review.BMC surgery · 2020Pooled it
- Noninvasive Tests for Liver Fibrosis Predict Postoperative Complications After Resection of Colorectal Liver Metastases.Annals of surgical oncology · 2026Article
- Review
- Multi-dimensional analysis reveals the potential of PDK4 as a tumor biomarker and target for immunotherapy.Discover oncology · 2026Article
- Article
- Interplay Between mFrontiers in cell and developmental biology · 2022Review
- Altered glycolysis results in drug-resistant in clinical tumor therapy.Oncology letters · 2021Review
- Pyruvate dehydrogenase kinases (PDKs): an overview toward clinical applications.Bioscience reports · 2021Review
- Article
- LncRNA SNHG17 Contributes to Proliferation, Migration, and Poor Prognosis of Hepatocellular Carcinoma.Canadian journal of gastroenterology & hepatology · 2021Article
- The Role of Neoadjuvant Chemotherapy in Locally Advanced Colon Cancer.Cancer management and research · 2021Review
- The Implications of PDK1-4 on Tumor Energy Metabolism, Aggressiveness and Therapy Resistance.Frontiers in oncology · 2020Review
- The double inhibition of PDK1 and STAT3-Y705 prevents liver metastasis in colorectal cancer.Scientific reports · 2019Article
- Protein Hydroxylation by Hypoxia-Inducible Factor (HIF) Hydroxylases: Unique or Ubiquitous?Cells · 2019Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPatients with borderline resectable colorectal liver metastases (CRLM) frequently receive neoadjuvant chemotherapy (NC) to reduce tumour burden, thus making surgical resection feasible. Even though NC can induce severe liver injury, most studies investigating tissue-based prognostic markers focus on tumour tissue. Here, we assessed the prognostic significance of pyruvate-dehydrogenase-kinase isoenzyme 4 (PDK4) within liver tissue of patients undergoing surgical resection due to CRLM.
methodsTranscript levels of hypoxia-adaptive genes (such as PDK isoenzymes) were assessed in the tissue of healthy liver, corresponding CRLM, healthy colon mucosa and corresponding tumour. Uni- and multivariate analyses were performed. Responses to chemotherapy upon up- or down-regulation of PDK4 were studied in vitro.
resultsPDK4 expression within healthy liver tissue was associated with increased overall survival and liver function following surgical resection of CRLM. This association was enhanced in patients with NC. PDK4 expression in CRLM tissue did not correlate with overall survival. Up-regulation of PDK4 increased the resistance of hepatocytes and colon cancer cells against chemotherapy-induced toxicity, whereas knockdown of PDK4 enhanced chemotherapy-associated cell damage.
conclusionOur findings suggest that up-regulated PDK4 expression reduces hepatic chemotherapy-induced oxidative stress and is associated with improved postoperative liver function in patients undergoing multimodal treatment and resection of CRLM.
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