Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients
Introduction NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) is known to be an orphan nuclear receptor that has been characterized as an intracellular immune checkpoint in effector T cells and, therefore, may control tumor development and growth. The prognostic impact of NR2...
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| Veröffentlicht in: | Journal of cancer research and clinical oncology 2023-08, Vol.149 (10), p.7155-7164 |
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| creator | Proppe, L. Jagomast, T. Beume, S. Klapper, L. Gitas, G. Köster, F. Perner, S. Rody, A. Ribbat-Idel, J. Hanker, L. C. |
| description | Introduction
NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) is known to be an orphan nuclear receptor that has been characterized as an intracellular immune checkpoint in effector T cells and, therefore, may control tumor development and growth. The prognostic impact of NR2F6 in endometrial cancers is evaluated in this study.
Materials and methods
Expression analysis of NR2F6 in 142 endometrial cancer patients was performed by immunohistochemistry of primary paraffin‑embedded tumor samples. Staining intensity of positive tumor cells was automatically assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival.
Results
Forty five of 116 evaluable samples (38.8%) showed an overexpression of NR2F6. This leads to an improvement of the overall survival (OS) and progression-free survival (PFS). In NR2F6-positive patients, the estimated mean OS was 156.9 months (95% confidence interval (CI) 143.1–170.7) compared to 106.2 months in NR2F6-negative patients (95% CI 86.2–126.3;
p
= 0.022). The estimated PFS differed by 63 months (152 months (95% CI 135.7–168.4) vs. 88.3 months (95% CI 68.5–108.0),
p
= 0.002). Furthermore, we found significant associations between NR2F6 positivity, MMR status, and PD1 status. A multivariate analysis suggests NR2F6 to be an independent factor influencing the OS (
p
= 0.03).
Conclusion
In this study, we could demonstrate that there is a longer progression-free and overall survival for NR2F6-positive patients with endometrial cancer. We conclude that NR2F6 might play an essential role in endometrial cancers. Further studies are required to validate its prognostic impact. |
| doi_str_mv | 10.1007/s00432-023-04632-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10374721</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2842692941</sourcerecordid><originalsourceid>FETCH-LOGICAL-c459t-2ec0a97bb19c4129cbee3cba266e7fb366859422b9e229df21b1dc95381785c03</originalsourceid><addsrcrecordid>eNqFks9u1DAQxi0EokvhBTggS1y4BOyxE8cnhCoKSBWVEJwtx5nsukrsYCcLvAZPjLdbyp8DnOzx_Oab8egj5DFnzzlj6kVmTAqoGIiKyabc4A7Z8MMTF6K-SzaMK17VwJsT8iDnK1biWsF9ciKatpWc1xvy_XKPCb_OCXP2MdA40GWHNKZ5ZwMNqxvRJprQ4bzERN9_gPOG-kxtztF5u2BPv_hlR_00p7gvUV7T3u_tSK1LMWc6xRHdOhaRvHbbFNc5Ux8ohj5OuCRfSGeDw0Rnu3gMS35I7g12zPjo5jwln85ffzx7W11cvnl39uqicrLWSwXomNWq67h2koN2HaJwnYWmQTV0omnaWkuATiOA7gfgHe-drkXLVVs7Jk7Jy6PuvHYT9q70TnY0c_KTTd9MtN78mQl-Z7ZxbzgTSirgReHZjUKKn1fMi5l8djiONmBcsxFMMqmUlPK_KKhWtkKJ-jDX07_Qq7imUFZhoJXQaNDy0BuO1PWaEw63g3NmDvYwR3uYYg9zbQ8DpejJ71--LfnphwKII5BLKmwx_er9D9kfKafI-Q</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2842692941</pqid></control><display><type>article</type><title>Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Proppe, L. ; Jagomast, T. ; Beume, S. ; Klapper, L. ; Gitas, G. ; Köster, F. ; Perner, S. ; Rody, A. ; Ribbat-Idel, J. ; Hanker, L. C.</creator><creatorcontrib>Proppe, L. ; Jagomast, T. ; Beume, S. ; Klapper, L. ; Gitas, G. ; Köster, F. ; Perner, S. ; Rody, A. ; Ribbat-Idel, J. ; Hanker, L. C.</creatorcontrib><description>Introduction
NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) is known to be an orphan nuclear receptor that has been characterized as an intracellular immune checkpoint in effector T cells and, therefore, may control tumor development and growth. The prognostic impact of NR2F6 in endometrial cancers is evaluated in this study.
Materials and methods
Expression analysis of NR2F6 in 142 endometrial cancer patients was performed by immunohistochemistry of primary paraffin‑embedded tumor samples. Staining intensity of positive tumor cells was automatically assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival.
Results
Forty five of 116 evaluable samples (38.8%) showed an overexpression of NR2F6. This leads to an improvement of the overall survival (OS) and progression-free survival (PFS). In NR2F6-positive patients, the estimated mean OS was 156.9 months (95% confidence interval (CI) 143.1–170.7) compared to 106.2 months in NR2F6-negative patients (95% CI 86.2–126.3;
p
= 0.022). The estimated PFS differed by 63 months (152 months (95% CI 135.7–168.4) vs. 88.3 months (95% CI 68.5–108.0),
p
= 0.002). Furthermore, we found significant associations between NR2F6 positivity, MMR status, and PD1 status. A multivariate analysis suggests NR2F6 to be an independent factor influencing the OS (
p
= 0.03).
Conclusion
In this study, we could demonstrate that there is a longer progression-free and overall survival for NR2F6-positive patients with endometrial cancer. We conclude that NR2F6 might play an essential role in endometrial cancers. Further studies are required to validate its prognostic impact.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-023-04632-2</identifier><identifier>PMID: 36884115</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Cancer ; Cancer Research ; confidence interval ; Effector cells ; Endometrial cancer ; Endometrial Neoplasms - genetics ; Endometrium ; Female ; Hematology ; Humans ; Immune checkpoint ; Immunohistochemistry ; Internal Medicine ; Lymphocytes T ; Medicine ; Medicine & Public Health ; Multivariate analysis ; Oncology ; orphan nuclear receptors ; Orphan Nuclear Receptors - metabolism ; Paraffin ; PD-1 protein ; Prognosis ; Repressor Proteins ; subfamily ; T-Lymphocytes - metabolism ; Tumor cells ; Tumors ; uterine neoplasms</subject><ispartof>Journal of cancer research and clinical oncology, 2023-08, Vol.149 (10), p.7155-7164</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c459t-2ec0a97bb19c4129cbee3cba266e7fb366859422b9e229df21b1dc95381785c03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00432-023-04632-2$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00432-023-04632-2$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36884115$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Proppe, L.</creatorcontrib><creatorcontrib>Jagomast, T.</creatorcontrib><creatorcontrib>Beume, S.</creatorcontrib><creatorcontrib>Klapper, L.</creatorcontrib><creatorcontrib>Gitas, G.</creatorcontrib><creatorcontrib>Köster, F.</creatorcontrib><creatorcontrib>Perner, S.</creatorcontrib><creatorcontrib>Rody, A.</creatorcontrib><creatorcontrib>Ribbat-Idel, J.</creatorcontrib><creatorcontrib>Hanker, L. C.</creatorcontrib><title>Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients</title><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><addtitle>J Cancer Res Clin Oncol</addtitle><description>Introduction
NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) is known to be an orphan nuclear receptor that has been characterized as an intracellular immune checkpoint in effector T cells and, therefore, may control tumor development and growth. The prognostic impact of NR2F6 in endometrial cancers is evaluated in this study.
Materials and methods
Expression analysis of NR2F6 in 142 endometrial cancer patients was performed by immunohistochemistry of primary paraffin‑embedded tumor samples. Staining intensity of positive tumor cells was automatically assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival.
Results
Forty five of 116 evaluable samples (38.8%) showed an overexpression of NR2F6. This leads to an improvement of the overall survival (OS) and progression-free survival (PFS). In NR2F6-positive patients, the estimated mean OS was 156.9 months (95% confidence interval (CI) 143.1–170.7) compared to 106.2 months in NR2F6-negative patients (95% CI 86.2–126.3;
p
= 0.022). The estimated PFS differed by 63 months (152 months (95% CI 135.7–168.4) vs. 88.3 months (95% CI 68.5–108.0),
p
= 0.002). Furthermore, we found significant associations between NR2F6 positivity, MMR status, and PD1 status. A multivariate analysis suggests NR2F6 to be an independent factor influencing the OS (
p
= 0.03).
Conclusion
In this study, we could demonstrate that there is a longer progression-free and overall survival for NR2F6-positive patients with endometrial cancer. We conclude that NR2F6 might play an essential role in endometrial cancers. Further studies are required to validate its prognostic impact.</description><subject>Cancer</subject><subject>Cancer Research</subject><subject>confidence interval</subject><subject>Effector cells</subject><subject>Endometrial cancer</subject><subject>Endometrial Neoplasms - genetics</subject><subject>Endometrium</subject><subject>Female</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immune checkpoint</subject><subject>Immunohistochemistry</subject><subject>Internal Medicine</subject><subject>Lymphocytes T</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Multivariate analysis</subject><subject>Oncology</subject><subject>orphan nuclear receptors</subject><subject>Orphan Nuclear Receptors - metabolism</subject><subject>Paraffin</subject><subject>PD-1 protein</subject><subject>Prognosis</subject><subject>Repressor Proteins</subject><subject>subfamily</subject><subject>T-Lymphocytes - metabolism</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>uterine neoplasms</subject><issn>0171-5216</issn><issn>1432-1335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFks9u1DAQxi0EokvhBTggS1y4BOyxE8cnhCoKSBWVEJwtx5nsukrsYCcLvAZPjLdbyp8DnOzx_Oab8egj5DFnzzlj6kVmTAqoGIiKyabc4A7Z8MMTF6K-SzaMK17VwJsT8iDnK1biWsF9ciKatpWc1xvy_XKPCb_OCXP2MdA40GWHNKZ5ZwMNqxvRJprQ4bzERN9_gPOG-kxtztF5u2BPv_hlR_00p7gvUV7T3u_tSK1LMWc6xRHdOhaRvHbbFNc5Ux8ohj5OuCRfSGeDw0Rnu3gMS35I7g12zPjo5jwln85ffzx7W11cvnl39uqicrLWSwXomNWq67h2koN2HaJwnYWmQTV0omnaWkuATiOA7gfgHe-drkXLVVs7Jk7Jy6PuvHYT9q70TnY0c_KTTd9MtN78mQl-Z7ZxbzgTSirgReHZjUKKn1fMi5l8djiONmBcsxFMMqmUlPK_KKhWtkKJ-jDX07_Qq7imUFZhoJXQaNDy0BuO1PWaEw63g3NmDvYwR3uYYg9zbQ8DpejJ71--LfnphwKII5BLKmwx_er9D9kfKafI-Q</recordid><startdate>20230801</startdate><enddate>20230801</enddate><creator>Proppe, L.</creator><creator>Jagomast, T.</creator><creator>Beume, S.</creator><creator>Klapper, L.</creator><creator>Gitas, G.</creator><creator>Köster, F.</creator><creator>Perner, S.</creator><creator>Rody, A.</creator><creator>Ribbat-Idel, J.</creator><creator>Hanker, L. C.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20230801</creationdate><title>Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients</title><author>Proppe, L. ; Jagomast, T. ; Beume, S. ; Klapper, L. ; Gitas, G. ; Köster, F. ; Perner, S. ; Rody, A. ; Ribbat-Idel, J. ; Hanker, L. C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-2ec0a97bb19c4129cbee3cba266e7fb366859422b9e229df21b1dc95381785c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Cancer</topic><topic>Cancer Research</topic><topic>confidence interval</topic><topic>Effector cells</topic><topic>Endometrial cancer</topic><topic>Endometrial Neoplasms - genetics</topic><topic>Endometrium</topic><topic>Female</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immune checkpoint</topic><topic>Immunohistochemistry</topic><topic>Internal Medicine</topic><topic>Lymphocytes T</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Multivariate analysis</topic><topic>Oncology</topic><topic>orphan nuclear receptors</topic><topic>Orphan Nuclear Receptors - metabolism</topic><topic>Paraffin</topic><topic>PD-1 protein</topic><topic>Prognosis</topic><topic>Repressor Proteins</topic><topic>subfamily</topic><topic>T-Lymphocytes - metabolism</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>uterine neoplasms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Proppe, L.</creatorcontrib><creatorcontrib>Jagomast, T.</creatorcontrib><creatorcontrib>Beume, S.</creatorcontrib><creatorcontrib>Klapper, L.</creatorcontrib><creatorcontrib>Gitas, G.</creatorcontrib><creatorcontrib>Köster, F.</creatorcontrib><creatorcontrib>Perner, S.</creatorcontrib><creatorcontrib>Rody, A.</creatorcontrib><creatorcontrib>Ribbat-Idel, J.</creatorcontrib><creatorcontrib>Hanker, L. 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C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients</atitle><jtitle>Journal of cancer research and clinical oncology</jtitle><stitle>J Cancer Res Clin Oncol</stitle><addtitle>J Cancer Res Clin Oncol</addtitle><date>2023-08-01</date><risdate>2023</risdate><volume>149</volume><issue>10</issue><spage>7155</spage><epage>7164</epage><pages>7155-7164</pages><issn>0171-5216</issn><eissn>1432-1335</eissn><abstract>Introduction
NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) is known to be an orphan nuclear receptor that has been characterized as an intracellular immune checkpoint in effector T cells and, therefore, may control tumor development and growth. The prognostic impact of NR2F6 in endometrial cancers is evaluated in this study.
Materials and methods
Expression analysis of NR2F6 in 142 endometrial cancer patients was performed by immunohistochemistry of primary paraffin‑embedded tumor samples. Staining intensity of positive tumor cells was automatically assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival.
Results
Forty five of 116 evaluable samples (38.8%) showed an overexpression of NR2F6. This leads to an improvement of the overall survival (OS) and progression-free survival (PFS). In NR2F6-positive patients, the estimated mean OS was 156.9 months (95% confidence interval (CI) 143.1–170.7) compared to 106.2 months in NR2F6-negative patients (95% CI 86.2–126.3;
p
= 0.022). The estimated PFS differed by 63 months (152 months (95% CI 135.7–168.4) vs. 88.3 months (95% CI 68.5–108.0),
p
= 0.002). Furthermore, we found significant associations between NR2F6 positivity, MMR status, and PD1 status. A multivariate analysis suggests NR2F6 to be an independent factor influencing the OS (
p
= 0.03).
Conclusion
In this study, we could demonstrate that there is a longer progression-free and overall survival for NR2F6-positive patients with endometrial cancer. We conclude that NR2F6 might play an essential role in endometrial cancers. Further studies are required to validate its prognostic impact.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>36884115</pmid><doi>10.1007/s00432-023-04632-2</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of cancer research and clinical oncology, 2023-08, Vol.149 (10), p.7155-7164 |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Cancer Cancer Research confidence interval Effector cells Endometrial cancer Endometrial Neoplasms - genetics Endometrium Female Hematology Humans Immune checkpoint Immunohistochemistry Internal Medicine Lymphocytes T Medicine Medicine & Public Health Multivariate analysis Oncology orphan nuclear receptors Orphan Nuclear Receptors - metabolism Paraffin PD-1 protein Prognosis Repressor Proteins subfamily T-Lymphocytes - metabolism Tumor cells Tumors uterine neoplasms |
| title | Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients |
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