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

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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.

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Proppe, L., Jagomast, T., Beume, S., Klapper, L., Gitas, G., Köster, F., … Hanker, L. C. (2023). Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients. Journal of Cancer Research and Clinical Oncology, 149(10), 7155–7164. https://doi.org/10.1007/s00432-023-04632-2

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