To discover early molecular markers for predicting the recurrence and metastasis of breast cancer, thereby guiding precise and personalized clinical treatment.

Utilizing the GSE9574 dataset from the GEO Database, we conducted differential gene analysis and GO/KEGG pathway analyses, using R 4.3.3 software. We applied Cytoscape MCODE to identify key seed genes associated with recurrence and metastasis and explored the relationship between these seed genes and clinicopathological features of breast cancer using the ONCOMINE database. The Kaplan-Meier method was used to examine the association between seed gene expression and recurrence-free survival (RFS), distant metastasis-free survival(DMFS) and overall survival(OS).

Analysis of the GSE9574 dataset revealed 207 differential genes, including 128 down-regulated genes and 79 up-regulated genes. NR4A2 emerged as the seed gene for the highest connectivity. Compared with normal breast tissues, NR4A2 expression was significantly lower in breast cancer tissues, especially in young patients and the patients with triple-negative subtypes, stage IV and metastatic breast cancer. Patients with low NR4A2 expression exhibited significantly lower 10-year RFS compared with patients with high NR4A2 expression (13.82% vs 15.27%, HR=0.81, 95%CI: 0.73-0.89, P<0.01) and 10-year DMFS (14.38% vs 17.96%, HR=0.80, 95%CI: 0.68-0.93, P<0.01). The 10-year overall survival showed no significant difference between two groups (18.17% vs 26.12%, HR=0.86, 95%CI: 0.71-1.04, P=0.12).

High expression of NR4A2 may indicate early molecular alteration in relapsed breast cancer. NR4A2 can be used as an early molecular marker for predicting breast cancer recurrence and metastasis.