Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Fechter, K; Feichtinger, J; Prochazka, K; Unterluggauer, JJ; Pansy, K; Steinbauer, E; Pichler, M; Haybaeck, J; Prokesch, A; Greinix, HT; Beham-Schmid, C; Neumeister, P; Thallinger, GG; Deutsch, AJA.
Cytoplasmic location of NR4A1 in aggressive lymphomas is associated with a favourable cancer specific survival.
Sci Rep. 2018; 8(1):14528-14528
Doi: 10.1038/s41598-018-32972-4
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- Führende Autor*innen der Med Uni Graz
- Deutsch Alexander
- Fechter Karoline
- Feichtinger Julia
- Co-Autor*innen der Med Uni Graz
- Beham-Schmid Christine
- Greinix Hildegard
- Haybäck Johannes
- Neumeister Peter
- Pansy Katrin
- Pichler Martin
- Prochazka Katharina
- Prokesch Andreas
- Steinbauer Elisabeth
- Unterluggauer Julia Judith
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- Abstract:
- The nuclear orphan receptor NR4A1 functions as tumour suppressor in aggressive lymphomas by pro-apoptotic genomic and non-genomic effects. Here, we immunohistochemically studied the clinico-pathological relevance of NR4A1 protein expression patterns in a cohort of 60 diffuse large B cell lymphoma (DLBCL) patients and non-neoplastic lymph nodes. We observed a significant association between high cytoplasmic NR4A1 and favourable cancer-specific survival and the germinal centre B cell-like subtype, respectively. Moreover, the percentage of lymphoma cells exhibiting cytoplasmic NR4A1 significantly correlated to those showing cleaved caspase 3. Complementary, functional profiling using gene set enrichment of Reactome pathways based on publicly available microarray data was applied to determine pathways potentially implicated in cytoplasmic localization of NR4A1 and validated by means of semi quantitative real-time PCR. The pathway analysis revealed changes in the ERK1/2 pathway, and this was corroborated by the finding that high cytoplasmic NR4A1 was associated with higher expression of ERK1/2 targets in our cohort. These data indicate that high cytoplasmic NR4A1 is associated with a favourable lymphoma-specific survival and highlights the importance of NR4A1 expression patterns as potential prognostic marker for risk assessment in aggressive lymphomas.