Abstract 246P
Background
Breast cancer is the second leading cause of cancer death in women. Although numerous potential biomarkers have been identified, but only several have been utilized in practical use. Hence, identification of new biomarkers is still urgently needed in the diagnostic workup and treatment of breast cancer. The RAD51 protein involves in recombinational repair of DNA breaks, which mutations have been detected in different cancers including breast cancers. However, the prognostic significance of RAD51 gene expression in breast cancer required further investigation.
Methods
We performed a systematic analysis of published annotated breast cancer transcriptomic data (DNA microarray, n=11,359) and RNA-seq (n=4,421) in bc-GenExMiner database for RAD51 expression. Other databases including PrognoScan, Search Tool for the Retrieval of Interacting Genes (STRING), Cytoscape, and cBioPortal were also used to study the prognostic role of RAD51 expression as well as its alteration in patient with breast cancer.
Results
RAD51 is found to be highly expressed in (A) in basal-like, HER2-E, and luminal B compared with normal-like subtype and (B) in BRCA1 mutated patients compared to wildtype BRCA1/2 and BRCA2-mutated patients. Forest plot showed RAD51 expression was correlated with disease specific survival, DSS (hazard ratio, HR=2.36, 95% confidence interval, CI=1.50-3.72; P=0.0002), overall survival, OS (HR=2.13, 95% CI=1.24-3.67; P=0.006494), disease-free survival, DFS (HR= 2.08, 95% CI=1.48-2.93; P=0.000028), and distance metastasis free survival, DMFS (HR=1.62, 95% CI=1.17-2.24; P=0.003404). The prognostic significance of RAD51 expression level as well as clinicopathological factors in breast cancer, including patient age, lymph node status, tumor size, tumor grade, estrogen and progesterone receptors, were evaluated by Cox regression model and revealed RAD51 expression was significantly associated with DMFS, DSS and DFS. Taken together, patients with high expression of BARD1 are more likely to have worse prognosis.
Conclusions
In conclusion, RAD51 might be a promising predictive biomarker for prognosis of breast cancer. However, in-depth experiments are needed to investigate the molecular mechanism of these results.
Editorial acknowledgement
This research was funded by the Malaysian Ministry of Higher Education through Fundamental Research Grant Scheme (FRGS/1/2020/SKK0/TAYLOR/02/2).
Legal entity responsible for the study
The authors.
Funding
Ministry of Education Malaysia (FRGS/1/2020/SKK0/TAYLOR/02/2).
Disclosure
All authors have declared no conflicts of interest.