Cytoplasmic location of NR4A1 in aggressive lymphomas is associated with a favourable cancer specific survival

Karoline Fechter, Julia Feichtinger, Katharina Prochazka, Julia Judith Unterluggauer, Katrin Pansy, Elisabeth Steinbauer, Martin Pichler, Johannes Haybaeck, Andreas Prokesch, Hildegard T Greinix, Christine Beham-Schmid, Peter Neumeister, Gerhard G Thallinger, Alexander J A Deutsch

Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

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.

Originalspracheenglisch
Aufsatznummer14528
FachzeitschriftScientific reports
Jahrgang8
Ausgabenummer1
DOIs
PublikationsstatusVeröffentlicht - 28 Sep 2018

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Lymphoma
Survival
Nuclear Receptor Subfamily 4, Group A, Member 1
Neoplasms
Germinal Center
Lymphoma, Large B-Cell, Diffuse
MAP Kinase Signaling System
Caspase 3
Real-Time Polymerase Chain Reaction
B-Lymphocytes
Lymph Nodes
Genes
Proteins

Fields of Expertise

  • Human- & Biotechnology
  • Information, Communication & Computing

Treatment code (Nähere Zuordnung)

  • Basic - Fundamental (Grundlagenforschung)

Kooperationen

  • BioTechMed-Graz

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Fechter, K., Feichtinger, J., Prochazka, K., Unterluggauer, J. J., Pansy, K., Steinbauer, E., ... Deutsch, A. J. A. (2018). Cytoplasmic location of NR4A1 in aggressive lymphomas is associated with a favourable cancer specific survival. Scientific reports, 8(1), [14528]. https://doi.org/10.1038/s41598-018-32972-4

Cytoplasmic location of NR4A1 in aggressive lymphomas is associated with a favourable cancer specific survival. / Fechter, Karoline; Feichtinger, Julia; Prochazka, Katharina; Unterluggauer, Julia Judith; Pansy, Katrin; Steinbauer, Elisabeth; Pichler, Martin; Haybaeck, Johannes; Prokesch, Andreas; Greinix, Hildegard T; Beham-Schmid, Christine; Neumeister, Peter; Thallinger, Gerhard G; Deutsch, Alexander J A.

in: Scientific reports, Jahrgang 8, Nr. 1, 14528, 28.09.2018.

Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

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 2018, 'Cytoplasmic location of NR4A1 in aggressive lymphomas is associated with a favourable cancer specific survival' Scientific reports, Jg. 8, Nr. 1, 14528. https://doi.org/10.1038/s41598-018-32972-4
Fechter K, Feichtinger J, Prochazka K, Unterluggauer JJ, Pansy K, Steinbauer E et al. Cytoplasmic location of NR4A1 in aggressive lymphomas is associated with a favourable cancer specific survival. Scientific reports. 2018 Sep 28;8(1). 14528. https://doi.org/10.1038/s41598-018-32972-4
Fechter, Karoline ; Feichtinger, Julia ; Prochazka, Katharina ; Unterluggauer, Julia Judith ; Pansy, Katrin ; Steinbauer, Elisabeth ; Pichler, Martin ; Haybaeck, Johannes ; Prokesch, Andreas ; Greinix, Hildegard T ; Beham-Schmid, Christine ; Neumeister, Peter ; Thallinger, Gerhard G ; Deutsch, Alexander J A. / Cytoplasmic location of NR4A1 in aggressive lymphomas is associated with a favourable cancer specific survival. in: Scientific reports. 2018 ; Jahrgang 8, Nr. 1.
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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.",
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AU - Pichler, Martin

AU - Haybaeck, Johannes

AU - Prokesch, Andreas

AU - Greinix, Hildegard T

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AU - Neumeister, Peter

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