Low NR3C2 levels correlate with aggressive features and poor prognosis in non-distant metastatic clear-cell renal cell carcinoma.

Abstract

NR3C2 has previously been described as a tumor suppressor gene in several cancers; however the prognostic significance and biological function of NR3C2 in patients with non-metastatic clear cell renal cell carcinoma (ccRCC) remain largely unclear. The prognostic value of NR3C2 expression was evaluated using data from The Cancer Genome Atlas (TCGA) and 181 patients with non-metastatic ccRCC undergoing nephrectomy in our center. Predictive nomograms were generated and identified independent prognosticators to assess ccRCC patient overall survival (OS) and progression free survival (PFS) at 1, 5, and 8 years. The functional involvement of NR3C2 in RCC was examined in both in vitro and in vivo models upon overexpression of NR3C2. NR3C2 was found to be downregulated in tumor tissues and was correlated with several clinicopathological parameters, including the T status (p <0.001) and histological Fuhrman grade (p = 0.002). Both Cox regression analysis and Kaplan-Meier survival curves showed that low NR3C2 expression correlated with poor OS (HR = 2.21, p = 0.014) and PFS (HR = 1.71, p = 0.051). The incorporation of NR3C2 status into the T stage, UISS, or SSIGN scores helps to refine individual risk stratification. The newly built nomograms involving NR3C2 expression could better predict OS and PFS. Overexpression of NR3C2 inhibited RCC cell proliferation, colony formation, invasion, migration, and vasculogenic mimicry in vitro and reduced the growth of RCC xenografts in vivo. Together, these results suggest that NR3C2 may serve as a potential prognostic factor in non-metastatic ccRCC patients after nephrectomy and is involved in RCC oncogenesis.