Differential Expression Of Boc, Spock2, And Gjd3 Is Associated With Brain Metastasis Of Er-Negative Breast Cancers

Simple Summary Brain metastasis is diagnosed in 30-50% of metastatic breast cancer patients with currently limited treatment strategies and usually short survival rates. In the present study, we aim to identify genes specifically associated with the development of brain metastasis in breast cancer. Therefore, we compared RNA expression profiles from two groups of patients with metastatic breast cancer, with and without brain involvement. Three genes BOC, SPOCK2, and GJD3 were overexpressed in the group of primary breast cancers which developed brain metastasis. Expression profiles were confirmed in an independent breast cancer cohort for both BOC and SPOCK2. In addition, differential overexpression of SPOCK2 and GJD3 mRNA levels were found to be associated with the development of brain metastasis in an external online database of 204 primary breast cancers. Verification of these genes as biomarkers for brain metastasis development in primary breast cancer is warranted. Background: Brain metastasis is considered one of the major causes of mortality in breast cancer patients. To invade the brain, tumor cells need to pass the blood-brain barrier by mechanisms that are partially understood. In primary ER-negative breast cancers that developed brain metastases, we found that some of the differentially expressed genes play roles in the T cell response. The present study aimed to identify genes involved in the formation of brain metastasis independently from the T cell response. Method: Previously profiled primary breast cancer samples were reanalyzed. Genes that were found to be differentially expressed were confirmed by RT-PCR and by immunohistochemistry using an independent cohort of samples. Results: BOC, SPOCK2, and GJD3 were overexpressed in the primary breast tumors that developed brain metastasis. BOC expression was successfully validated at the protein level. SPOCK2 was validated at both mRNA and protein levels. SPOCK2 and GJD3 mRNA overexpression were also found to be associated with cerebral metastasis in an external online database consisting of 204 primary breast cancers. Conclusion: The overexpression of BOC, SPOCK2, and GJD3 is associated with the invasion of breast cancer into the brain. Further studies to determine their specific function and potential value as brain metastasis biomarkers are required.