ArticlePloS one2013
Loss of TRAIL-receptors is a recurrent feature in pancreatic cancer and determines the prognosis of patients with no nodal metastasis after surgery.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- TRAIL predisposes non-small cell lung cancer to ferroptosis by regulating ASK-1/JNK1 pathway.Discover oncology · 2024Article
- TRAIL Receptor Targeting Agents Potentiate PARP Inhibitor Efficacy in Pancreatic Cancer Independently ofCancers · 2022Article
- TRAIL receptors are expressed in both malignant and stromal cells in pancreatic ductal adenocarcinoma.American journal of cancer research · 2021Article
- Heterogeneous intracellular TRAIL-receptor distribution predicts poor outcome in breast cancer patients.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Soluble TRAIL Armed Human MSC As Gene Therapy For Pancreatic Cancer.Scientific reports · 2019Article
- Article
- Cytoplasmic TRAIL-R1 is a positive prognostic marker in PDAC.BMC cancer · 2018Article
- HuR Contributes to TRAIL Resistance by Restricting Death Receptor 4 Expression in Pancreatic Cancer Cells.Molecular cancer research : MCR · 2016Article
- Inactivation of BRCA2 in human cancer cells identifies a subset of tumors with enhanced sensitivity towards death receptor-mediated apoptosis.Oncotarget · 2016Article
- Article
- Small molecule inhibitor YM155-mediated activation of death receptor 5 is crucial for chemotherapy-induced apoptosis in pancreatic carcinoma.Molecular cancer therapeutics · 2015Article
- Regulation of TRAIL-receptor expression by the ubiquitin-proteasome system.International journal of molecular sciences · 2014Review
- Compartmentalization of TNF-related apoptosis-inducing ligand (TRAIL) death receptor functions: emerging role of nuclear TRAIL-R2.Cell death & disease · 2014Review
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9 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
introductionAgonistic antibodies targeting TRAIL-receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are being developed as a novel therapeutic approach in cancer therapy including pancreatic cancer. However, the cellular distribution of these receptors in primary pancreatic cancer samples has not been sufficiently investigated and no study has yet addressed the issue of their prognostic significance in this tumor entity. AIMS AND
methodsApplying tissue microarray (TMA) analysis, we performed an immunohistochemical assessment of TRAIL-receptors in surgical samples from 84 consecutive patients affected by pancreatic adenocarcinoma and in 26 additional selected specimens from patients with no lymph nodes metastasis at the time of surgery. The prognostic significance of membrane staining and staining intensity for TRAIL-receptors was evaluated.
resultsThe fraction of pancreatic cancer samples with positive membrane staining for TRAIL-R1 and TRAIL-R2 was lower than that of cells from surrounding non-tumor tissues (TRAIL-R1: p<0.001, TRAIL-R2: p = 0.006). In addition, subgroup analyses showed that loss of membrane staining for TRAIL-R2 was associated with poorer prognosis in patients without nodal metastases (multivariate Cox regression analysis, Hazard Ratio: 0.44 [95% confidence interval: 0.22-0.87]; p = 0.019). In contrast, analysis of decoy receptors TRAIL-R3 and -R4 in tumor samples showed an exclusively cytoplasmatic staining pattern and no prognostic relevance.
conclusionThis is a first report on the prognostic significance of TRAIL-receptors expression in pancreatic cancer showing that TRAIL-R2 might represent a prognostic marker for patients with early stage disease. In addition, our data suggest that loss of membrane-bound TRAIL-receptors could represent a molecular mechanism for therapeutic failure upon administration of TRAIL-receptors-targeting antibodies in pancreatic cancer. This hypothesis should be evaluated in future clinical trials.
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