Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients

• Published in: Journal of cancer research and clinical oncology Vol. 149; no. 10; pp. 7155 - 7164
• Main Authors: Proppe, L., Jagomast, T., Beume, S., Klapper, L., Gitas, G., Köster, F., Perner, S., Rody, A., Ribbat-Idel, J., Hanker, L. C.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2023; Springer Nature B.V
• Subjects: Cancer; Cancer Research; 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 - metabolism; Paraffin; PD-1 protein; Prognosis; Repressor Proteins; T-Lymphocytes - metabolism; Tumor cells; Tumors; Immune checkpoint inhibition; Endometrial cancer; Molecular subgroups; NR2F6
• DOI: 10.1007/s00432-023-04632-2
• ISSN: 0171-5216

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.