Bioinformatic analysis of prognostic value of ARAP3 in breast cancer and the associated signaling pathways.

OBJECTIVE: In this study, we tried to pool previous annotated genomic data to assess the association between ARAP3 expression and metastatic relapse (MR) risk in patients with breast cancer. Moreover, we also investigated the signaling pathways in which ARAP3 might be involved in breast cancer.

MATERIALS AND METHODS: The raw microarray data (GDS5666) that compared gene transcriptional profiles of 4T1 derived lung-aggressive explant and primary tumor explant were reanalyzed to identify the dysregulated genes. ARAP3 mRNA expression, its association with MR-free survival and its co-upregulated genes in breast cancer, were studied by data mining in TCGA database and Breast Cancer Gene-Expression Miner Version 4.0 (bc-GenExMiner 4.0).

RESULTS: ARAP3 is a significantly upregulated gene in the metastatic breast tumor cells. The ER- patients with high ARAP3 expression had significantly increased the risk of MR, regardless of the nodal status. Patients in ER-/Nm group with high ARAP3 expression had the highest risk of MR (HR: 1.25; 95%CI: 1.10-1.41, p<0.001). In patients with basal-like tumors, High ARAP3 level is associated with significantly worse MR-free survival (HR: 1.63, 95%CI: 1.22-2.19, p=0.001). ARAP3 might be closely related to the NOTCH4 and CDH5 signaling pathways in breast cancer.

CONCLUSIONS: The expression level of ARAP3 might be a useful indicator of the metastatic likelihood of the basal-like breast tumors. ARAP3 might be involved in NOTCH4 and CDH5 related signaling pathways, but the underlying mechanism should be further studied.