| Summary: | 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: <i>BOC, SPOCK2,</i> and <i>GJD3</i> were overexpressed in the primary breast tumors that developed brain metastasis. <i>BOC</i> expression was successfully validated at the protein level. <i>SPOCK2</i> was validated at both mRNA and protein levels. <i>SPOCK2</i> and <i>GJD3</i> 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 <i>BOC, SPOCK2</i>, and <i>GJD3</i> 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.
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