Introduction/Background NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) is known to be an orphan nuclear receptor being an intracellular immune checkpoint in effector T cells. It might play an essential role for tumor development and growth. Therefore, the prognostic impact of NR2F6 in endometrial cancer is evaluated in this study.

Methodology Expression analysis of NR2F6 in 142 endometrial cancer patients was performed by immunohistochemistry. Staining intensity of tumor cells was computerized assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival.

Results 46 of 117 evaluable samples (39.3%) showed an overexpression of NR2F6, leading to an improvement of the overall (OS) and disease-free survival (DFS). In NR2F6 positive patients, the mean OS was 156.6 months (95% confidence interval (CI): 142.4 – 170.8) compared to 105.8 months in NR2F6 negative patients (95% CI: 85.6 – 125.9; p = 0.025). The disease-free survival differed by 58.4 months (156 months (95% CI: 142.2 – 169.9) vs. 97.6 months (95% CI: 74.7 – 120.6), p = 0.004). 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 disease-free survival (p = 0.037).

Conclusion This is the first report on the prognostic impact of NR2F6 in endometrial cancer patients. We could demonstrate that there is a significant better progression-free and overall survival for patients with overexpression of NR2F6 in patients with endometrial cancer. Further studies are required to validate its prognostic impact.