Background:
Breast cancer bone
metastasis (BCBM)-specific genes have been reported without considering
biological differences based on
estrogen receptor (ER) status. The aims of this study were to identify BCBM-specific genes using our patient dataset and validate previously reported BCBM-specific genes, and to determine whether ER-status-related
biological differences matter in identification of BCBM-specific genes. Methods: We used Affymetrix GeneChips to analyze 365 primary
human epidermal growth factor receptor 2 (HER2)-negative invasive
breast cancer specimens. Genes that were differentially expressed between patients who developed bone
metastasis and those who developed non-bone
metastasis were identified using Cox proportional hazards model, and differential expression of gene sets was assessed using gene set analysis. We performed gene set analysis to determine whether
biological function associated with bone
metastasis were different by ER status using 2,246 functionally annotated gene sets assembled from Gene Ontology data base. Results: Among 16,712 probe sets, 592 were overexpressed in the bone
metastasis cohort compared to the non-bone-
metastasis cohort (false discovery rate ≤ 0.05). However, no BCBM-specific genes met our significance tests when the
cancers were stratified by ER status. In ER-positive and ER-negative breast
cancers, 151 and 125 gene sets, respectively, were overexpressed for BCBM and the majority of BCBM-related pathways were different. Of significant gene sets, only 13 gene sets were overlapped between ER-positive and -negative cohorts. Conclusion: ER-positive and ER-negative breast
cancers have different
biological pathways in BCBM development. We have yet to explore BCBM-related
biomarkers and targets considering the
biological features associated with BCBM depending on the ER status.