The expression and prognostic significance of circadian gene NR1D1/2 in patients with gastric cancer

Abstract Objective: The dysregulation of circadian rhythms is proved to be associated with the development of and may affect the treatment of tumors. However, the biological role of NR1D1/2 remains elusive in gastric cancer. We analyzed the effects of NR1D1/2 expression with occurrence and prognostic value for gastric cancer. Methods: By using the online databases including ULCAN, KM plotter, STRING database and FunRich software, the effects of NR1D1/2 on the occurrence, clinical features and prognosis of gastric cancer were evaluated in gastric cancer. Results: Based on the analyses of data obtained from online database, both the mRNA expression of NR1D1 and NR1D2 were higher in stomach carcinoma than in normal tissue (p<0.001). The level of NR1D1 expression was significantly increased in female patients, T, N, and Lauren classification in gastric cancer patients (p=0.017, 0.000, 0.014, 0.005, and 0.004), and the NR1D2 was significantly higher in male patients, HER2 status, tumor stage, T, Lauren classification, and differentiation in gastric cancer patients (p=0.000, 0.000, 0.000, 0.001, 0.000 and 0.000). The elevation of NR1D1/2 was significantly correlated with worse OS (overall survival), PPS (post-progression survival) and FP (First progression) in gastric cancer patients (p<0.001). Furthermore, we constructed protein-protein interaction networks of genes coexpressed with NR1D1 and NR1D2. FunRich analyses suggested that the NR1D1 and NR1D2 was possibly involved in BMAL1: CLOCK/NPAS2 activates gene expression and circadian clock pathway. Conclusion: Our study suggests that NR1D1 and NR1D2 may be potential biomarkers for the diagnosis and prognosis of gastric cancer.