Role of NR1D1 in Colorectal Cancer: Impact on Prognosis, Immune Microenvironment, and Oncogenic Pathways.

Abstract

Background: The goal was to explore the impact of the NR1D1 gene on the occurrence, development, and prognosis of colorectal cancer (CRC) using bioinformatics approaches.

Methods: CRC transcriptomic and clinical data from TCGA were analyzed to compare NR1D1 expression in tumors and various clinical stages. Survival differences between high and low NR1D1 expression groups were assessed using the R survival package. Univariate and multivariate Cox regression analyses identified independent prognostic factors, and a prognostic nomogram was constructed and evaluated via ROC and calibration curves. Differentially expressed genes were identified using the limma package, and functional enrichment was performed with clusterProfiler. The XCELL algorithm was used to evaluate differences in immune infiltration. Validation was conducted using GEO, HPA, qRT-PCR, and western blotting.

Results: NR1D1 is overexpressed in CRC and correlates with advanced clinical stages. High NR1D1 expression is associated with poor prognosis, with multivariate Cox regression identifying NR1D1, age, stage, and NM grade as independent prognostic factors. The constructed model showed good performance (AUC > 0.70) at 1, 3, and 5 years. Enrichment analysis revealed NR1D1-related genes enriched in pathways like systemic lupus erythematosus and neutrophil extracellular trap formation. The low NR1D1 expression group showed increased immune infiltration, higher immune scores, and elevated immune microenvironment scores. NR1D1 negatively correlated with immune checkpoints, with significant differences in gene expression between high and low NR1D1 samples. High NR1D1 expression in CRC was confirmed in the GSE39582 dataset and HPA database, correlating with poor prognosis and validated by qRT-PCR and western blotting.

Conclusions: NR1D1 may play a crucial oncogenic role in the occurrence and development of CRC.