Abstract
Ovarian cancer is known for its high recurrence rates and poor prognosis, primarily due to chemoresistance, which significantly limits treatment options. Grasping the processes that contribute to chemoresistance is essential for the advancement of more efficient therapy methods. Firstly, we discovered that nuclear receptor subfamily 1 group D member 2 (NR1D2) was significantly elevated in cisplatin-resistant ovarian cancer cells, as revealed by RNA sequencing. Subsequent study indicated that NR1D2 was highly expressed in chemo-resistant ovarian cancer samples than the chemo-sensitive group, and negatively correlated with ovarian cancer patients' survival. Moreover, NR1D2 silencing markedly contributed to cisplatin susceptibility of ovarian cancer cells. Additionally, the analysis of untargeted metabolomics mass spectrometry demonstrated a significant correlation between NR1D2 and the process of ferroptosis. Following this, we observed that NR1D2 silencing considerably increased the concentration of lipid peroxidation malondialdehyde (MDA) and ferrous ion, concomitant with downregulation of ferroptosis suppressor protein 1 (FSP1). Finally, the study revealed that NR1D2 influences immune infiltration in ovarian cancer. In summary, NR1D2 served as a prognostic biomarker in ovarian cancer and induced cisplatin-resistance. Furthermore, its expression was linked to ferroptosis and immune regulation within the tumor microenvironment. Targeting NR1D2 may provide a potential therapeutic strategy to enhance treatment efficacy in ovarian cancer.
Keywords:
Chemoresistance; Ferroptosis; Immune infiltration; NR1D2; Ovarian cancer.