ArticleBMC cancer2018
Cytoplasmic TRAIL-R1 is a positive prognostic marker in PDAC.
Article in BMC cancer, 2018. 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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13 citing papers in PubMed, 23 citations in OpenAlex.
- Homeobox protein B6 and homeobox protein B8 control immune-cancer cell interactions in pancreatic cancer.Molecular biomedicine · 2025Article
- Serum TRAIL predicts severity and prognosis in patients with community-acquired pneumonia: a prospective cohort study.Internal and emergency medicine · 2022Article
- Proteasome inhibition triggers the formation of TRAIL receptor 2 platforms for caspase-8 activation that accumulate in the cytosol.Cell death and differentiation · 2022Article
- Endogenous TRAIL-R4 critically impacts apoptotic and non-apoptotic TRAIL-induced signaling in cancer cells.Frontiers in cell and developmental biology · 2022Article
- A Substance P (SP)/Neurokinin-1 Receptor Axis Promotes Perineural Invasion of Pancreatic Cancer and Is Affected by lncRNA LOC389641.Journal of immunology research · 2022Article
- Prognostic significance of high mobility group A2 (HMGA2) in pancreatic ductal adenocarcinoma: malignant functions of cytoplasmic HMGA2 expression.Journal of cancer research and clinical oncology · 2021Article
- TRAIL receptors are expressed in both malignant and stromal cells in pancreatic ductal adenocarcinoma.American journal of cancer research · 2021Article
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- Necroptosis in pancreatic cancer promotes cancer cell migration and invasion by release of CXCL5.PloS one · 2020Article
- TRAIL Induces Nuclear Translocation and Chromatin Localization of TRAIL Death Receptors.Cancers · 2019Article
- The Hepatic Microenvironment and TRAIL-R2 Impact Outgrowth of Liver Metastases in Pancreatic Cancer after Surgical Resection.Cancers · 2019Article
- TRAIL-Receptor 4 Modulates γδ T Cell-Cytotoxicity Toward Cancer Cells.Frontiers in immunology · 2019Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe death receptors TRAIL-R1 and TRAIL-R2 are frequently overexpressed in cancer and there is an emerging evidence for their important role in malignant progression, also in the case of pancreatic ductal adenocarcinoma (PDAC). In their canonical localization at the plasma membrane, TRAIL-R1/-R2 may induce cell death and/or pro-inflammatory signaling leading to cell migration, invasion and metastasis. Although, they have repeatedly been found intracellular, in the cytoplasm and in the nucleus, their functions in intracellular locations are still not well understood. Likewise, studies dealing with the prognostic relevance of TRAIL-Rs located in particular cellular compartments are very rare. For PDAC, the correlation of nuclear TRAIL-R2 with worse patients' prognosis has been shown recently. Corresponding data on TRAIL-R1 are not available so far.
methodsIn the present study we analyzed the expression of TRAIL-R1 in 106 PDACs and 28 adjacent, peritumoral non-malignant pancreatic ducts with special emphasis on its cytoplasmic and nuclear localization and correlated the immunohistochemical findings with clinico-pathological patient characteristics.
resultsTRAIL-R1 was found in 93.4% of all PDAC samples. Cytoplasmic staining was present with very similar intensity in tumor and normal tissue. In contrast, nuclear TRAIL-R1 staining was significantly stronger in tumor compared to normal tissue (p = 0.006). Interestingly, we found that the number of cells with cytoplasmic TRAIL-R1 staining negatively correlates with tumor grading (p = 0.043). No such correlation could be detected for nuclear TRAIL-R1. Neither, cytoplasmic nor nuclear TRAIL-R1 staining showed a correlation with other clinico-pathological parameter such as pTNM categories. However, Kaplan-Meier analyses revealed significantly prolonged median survival of patients with positive cytoplasmic TRAIL-R1 expression in more than 80% of tumor cells compared to patients with tumors containing a smaller quantity of cells positively stained for cytoplasmic TRAIL-R1 (20 vs. 8 months; p = 0.004).
conclusionCytoplasmic TRAIL-R1 is a positive prognostic marker for patients with PDAC. Our findings indicate that loss of cytoplasmic TRAIL-R1 results in recurrent disease with more malignant phenotype thus suggesting anti-tumor activities of cytoplasmic TRAIL-R1 in PDAC.
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