Correlation of NRF2 and progesterone receptor and its effects on ovarian cancer biology
Identifieur interne : 000924 ( Main/Exploration ); précédent : 000923; suivant : 000925Correlation of NRF2 and progesterone receptor and its effects on ovarian cancer biology
Auteurs : Bastian Czogalla [Allemagne] ; Maja Kahaly [Allemagne] ; Doris Mayr [Allemagne] ; Elisa Schmoeckel [Allemagne] ; Beate Niesler [Allemagne] ; Anna Hester [Allemagne] ; Christine Zeder-Gö [Allemagne] ; Thomas Kolben [Allemagne] ; Alexander Burges [Allemagne] ; Sven Mahner [Allemagne] ; Udo Jeschke [Allemagne] ; Fabian Trillsch [Allemagne]Source :
- Cancer Management and Research [ 1179-1322 ] ; 2019.
Abstract
This study aimed to investigate the potential prognostic impact of nuclear factor erythroid 2-related factor 2 (NRF2) and progesterone receptor A (PRA)/progesterone receptor B (PRB) in ovarian cancer patients which might be the rationale for putative new treatment strategies.
The presence of NRF2 and PRA/PRB was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC). Staining of NRF2 and PRA/PRB was rated using the semi-quantitative immunoreactive score (IR score, Remmele’s score) and correlated to clinical and pathological data. NRF2 and PRA/PRB expression were compared with respect to the overall survival (OS).
NRF2 staining was different in both, the cytoplasm and nucleus between the histological subtypes (
In this study, the combination of cytoplasmic NRF2 and high PRA/PRB expression was demonstrated to be associated with improved overall survival in ovarian cancer patients. Further understanding of interactions within the NRF2/AKR1C1/PR pathway could open new additional therapeutic approaches.
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DOI: 10.2147/CMAR.S210004
PubMed: 31616183
PubMed Central: 6699153
Affiliations:
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strict</wicri:regionArea></affiliation></author><author><name sortKey="Zeder Go, Christine" sort="Zeder Go, Christine" uniqKey="Zeder Go C" first="Christine" last="Zeder-Gö">Christine Zeder-Gö</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kolben, Thomas" sort="Kolben, Thomas" uniqKey="Kolben T" first="Thomas" last="Kolben">Thomas Kolben</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country 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strict</wicri:regionArea></affiliation></author><author><name sortKey="Jeschke, Udo" sort="Jeschke, Udo" uniqKey="Jeschke U" first="Udo" last="Jeschke">Udo Jeschke</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Trillsch, Fabian" sort="Trillsch, Fabian" uniqKey="Trillsch F" first="Fabian" last="Trillsch">Fabian Trillsch</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country 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type="wicri:Area/Main/Curation">000924</idno><idno type="wicri:Area/Main/Exploration">000924</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Correlation of NRF2 and progesterone receptor and its effects on ovarian cancer biology</title><author><name sortKey="Czogalla, Bastian" sort="Czogalla, Bastian" uniqKey="Czogalla B" first="Bastian" last="Czogalla">Bastian Czogalla</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kahaly, Maja" sort="Kahaly, Maja" uniqKey="Kahaly M" first="Maja" last="Kahaly">Maja Kahaly</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mayr, Doris" sort="Mayr, Doris" uniqKey="Mayr D" first="Doris" last="Mayr">Doris Mayr</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Faculty of Medicine, Institute of Pathology, Lmu Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Schmoeckel, Elisa" sort="Schmoeckel, Elisa" uniqKey="Schmoeckel E" first="Elisa" last="Schmoeckel">Elisa Schmoeckel</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Faculty of Medicine, Institute of Pathology, Lmu Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Niesler, Beate" sort="Niesler, Beate" uniqKey="Niesler B" first="Beate" last="Niesler">Beate Niesler</name><affiliation wicri:level="1"><nlm:aff id="AFF0003"><institution>Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg</institution>,<addr-line>Heidelberg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hester, Anna" sort="Hester, Anna" uniqKey="Hester A" first="Anna" last="Hester">Anna Hester</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zeder Go, Christine" sort="Zeder Go, Christine" uniqKey="Zeder Go C" first="Christine" last="Zeder-Gö">Christine Zeder-Gö</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kolben, Thomas" sort="Kolben, Thomas" uniqKey="Kolben T" first="Thomas" last="Kolben">Thomas Kolben</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Burges, Alexander" sort="Burges, Alexander" uniqKey="Burges A" first="Alexander" last="Burges">Alexander Burges</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mahner, Sven" sort="Mahner, Sven" uniqKey="Mahner S" first="Sven" last="Mahner">Sven Mahner</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jeschke, Udo" sort="Jeschke, Udo" uniqKey="Jeschke U" first="Udo" last="Jeschke">Udo Jeschke</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Trillsch, Fabian" sort="Trillsch, Fabian" uniqKey="Trillsch F" first="Fabian" last="Trillsch">Fabian Trillsch</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Obstetrics and Gynecology, University Hospital, LMU Munich</institution>,<addr-line>Munich</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cancer Management and Research</title><idno type="eISSN">1179-1322</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S2001"><title>Purpose</title><p>This study aimed to investigate the potential prognostic impact of nuclear factor erythroid 2-related factor 2 (NRF2) and progesterone receptor A (PRA)/progesterone receptor B (PRB) in ovarian cancer patients which might be the rationale for putative new treatment strategies.</p></sec><sec id="S2002"><title>Patients and methods</title><p>The presence of NRF2 and PRA/PRB was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC). Staining of NRF2 and PRA/PRB was rated using the semi-quantitative immunoreactive score (IR score, Remmele’s score) and correlated to clinical and pathological data. NRF2 and PRA/PRB expression were compared with respect to the overall survival (OS).</p></sec><sec id="S2003"><title>Results</title><p>NRF2 staining was different in both, the cytoplasm and nucleus between the histological subtypes (<italic>p</italic>=0.001 and <italic>p</italic>=0.02, respectively). There was a significant difference in the PRA expression comparing all histological subtypes (<italic>p</italic>=0.02). Histological subtypes showed no significant differences in the PRB expression. A strong correlation of cytoplasmic NRF2 and PRA expression was detected (cc=0.247, <italic>p</italic>=0.003) as well as of cytoplasmic NRF2 and PRB expression (cc=0.25, <italic>p</italic>=0.003), confirmed by immunofluorescence double staining. Cytoplasmic NRF2 expression was associated with a longer OS (median 50.6 vs 32.5 months; <italic>p</italic>=0.1) as it was seen for PRA expression (median 63.4 vs 33.1 months; <italic>p</italic>=0.08), although not statistically significant. In addition, high PRB expression (median 80.4 vs 32.5 months; <italic>p</italic>=0.04) and concurrent expression of cytoplasmic NRF2 and PRA were associated with a significantly longer OS (median 109.7 vs 30.6 months; <italic>p</italic>=0.02). The same relationship was also noted for NRF2 and PRB with improved OS for patients expressing both cytoplasmic NRF2 and PRB (median 153.5 vs 30.6 months; <italic>p</italic>=0.009). Silencing of <italic>NFE2L2</italic> induced higher mRNA expression of <italic>PGR</italic> in the cancer cell line OVCAR3 (<italic>p</italic>>0.05) confirming genetic interactions of NRF2 and PR.</p></sec><sec id="S2004"><title>Conclusion</title><p>In this study, the combination of cytoplasmic NRF2 and high PRA/PRB expression was demonstrated to be associated with improved overall survival in ovarian cancer patients. Further understanding of interactions within the NRF2/AKR1C1/PR pathway could open new additional therapeutic approaches.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li></country></list><tree><country name="Allemagne"><noRegion><name sortKey="Czogalla, Bastian" sort="Czogalla, Bastian" uniqKey="Czogalla B" first="Bastian" last="Czogalla">Bastian Czogalla</name></noRegion><name sortKey="Burges, Alexander" sort="Burges, Alexander" uniqKey="Burges A" first="Alexander" last="Burges">Alexander Burges</name><name sortKey="Hester, Anna" sort="Hester, Anna" uniqKey="Hester A" first="Anna" last="Hester">Anna Hester</name><name sortKey="Jeschke, Udo" sort="Jeschke, Udo" uniqKey="Jeschke U" first="Udo" last="Jeschke">Udo Jeschke</name><name sortKey="Kahaly, Maja" sort="Kahaly, Maja" uniqKey="Kahaly M" first="Maja" last="Kahaly">Maja Kahaly</name><name sortKey="Kolben, Thomas" sort="Kolben, Thomas" uniqKey="Kolben T" first="Thomas" last="Kolben">Thomas Kolben</name><name sortKey="Mahner, Sven" sort="Mahner, Sven" uniqKey="Mahner S" first="Sven" last="Mahner">Sven Mahner</name><name sortKey="Mayr, Doris" sort="Mayr, Doris" uniqKey="Mayr D" first="Doris" last="Mayr">Doris Mayr</name><name sortKey="Niesler, Beate" sort="Niesler, Beate" uniqKey="Niesler B" first="Beate" last="Niesler">Beate Niesler</name><name sortKey="Schmoeckel, Elisa" sort="Schmoeckel, Elisa" uniqKey="Schmoeckel E" first="Elisa" last="Schmoeckel">Elisa Schmoeckel</name><name sortKey="Trillsch, Fabian" sort="Trillsch, Fabian" uniqKey="Trillsch F" first="Fabian" last="Trillsch">Fabian Trillsch</name><name sortKey="Zeder Go, Christine" sort="Zeder Go, Christine" uniqKey="Zeder Go C" first="Christine" last="Zeder-Gö">Christine Zeder-Gö</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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