C/EBP-Family Redundancy Determines Patient Survival and Lymph Node Involvement in PDAC
| Autor: | Leonie Hartl, Joris J. T. H. Roelofs, Frederike Dijk, Maarten F. Bijlsma, JanWillem Duitman, C. Arnold Spek |
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| Přispěvatelé: | Center of Experimental and Molecular Medicine, Graduate School, AII - Cancer immunology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, Pathology, ACS - Diabetes & metabolism, AII - Inflammatory diseases, Pulmonology, 01 Internal and external specialisms, Pulmonary medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Hartl, L, Roelofs, J J T H, Dijk, F, Bijlsma, M F, Duitman, J & Spek, C A 2023, ' C/EBP-Family Redundancy Determines Patient Survival and Lymph Node Involvement in PDAC ', International Journal of Molecular Sciences, vol. 24, no. 2, 1537 . https://doi.org/10.3390/ijms24021537 International journal of molecular sciences, 24(2):1537. Multidisciplinary Digital Publishing Institute (MDPI) International Journal of Molecular Sciences; Volume 24; Issue 2; Pages: 1537 International Journal of Molecular Sciences, 24(2):1537. Multidisciplinary Digital Publishing Institute (MDPI) |
| ISSN: | 1661-6596 |
| Popis: | Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with a poor clinical prognosis and unsatisfactory treatment options. We previously found that the transcription factor CCAAT/Enhancer-Binding Protein Delta (C/EBPδ) is lowly expressed in PDAC compared to healthy pancreas duct cells, and that patient survival and lymph node involvement in PDAC is correlated with the expression of C/EBPδ in primary tumor cells. C/EBPδ shares a homologous DNA-binding sequence with other C/EBP-proteins, leading to the presumption that other C/EBP-family members might act redundantly and compensate for the loss of C/EBPδ. This implies that patient stratification could be improved when expression levels of multiple C/EBP-family members are considered simultaneously. In this study, we assessed whether the quantification of C/EBPβ or C/EBPγ in addition to that of C/EBPδ might improve the prediction of patient survival and lymph node involvement using a cohort of 68 resectable PDAC patients. Using Kaplan–Meier analyses of patient groups with different C/EBP-expression levels, we found that both C/EBPβ and C/EBPγ can partially compensate for low C/EBPδ and improve patient survival. Further, we uncovered C/EBPβ as a novel predictor of a decreased likelihood of lymph node involvement in PDAC, and found that C/EBPβ and C/EBPδ can compensate for the lack of each other in order to reduce the risk of lymph node involvement. C/EBPγ, on the other hand, appears to promote lymph node involvement in the absence of C/EBPδ. Altogether, our results show that the redundancy of C/EBP-family members might have a profound influence on clinical prognoses and that the expression of both C/EPBβ and C/EBPγ should be taken into account when dichotomizing patients according to C/EBPδ expression. |
| Databáze: | OpenAIRE |
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