Research Article Open Access

The Expression and Prognostic Significance of Circadian Gene NR1D1/NR1D2 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 (Nuclear Receptor Subfamily 1, Group D, Member 1) NR1D1/NR1D2 (Nuclear Receptor Subfamily 1, Group D, Member 2) remains elusive in gastric cancer. We analyzed the effects of NR1D1/NR1D2 expression with occurrence and prognostic value for gastric cancer.

Methods: By using the online databases including UALCAN (The University of Alabama at Birmingham Cancer Data Analysis Portal), KM plotter (Kaplan-Meier plotter), STRING database and FunRich software, the effects of NR1D1/NR1D2 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 (Tumor), N (Nodes), M (Metastasis) 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/NR1D2 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 (Brain and Muscle ARNT-Like 1) BMAL1: CLOCK (Circadian Locomotor Output Cycles Kaput)/NPAS2 (Neuronal PAS Domain Protein 2) 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.

ZhiXue Zheng*, Xuan Cai, Jing Tao Bi, Ya Qi Liu

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