K. Takabe1, E. Katsuta1, A. A. Maawy1, L. Yan2 1Roswell Park Cancer Institute,Breast Surgery, Department Of Surgical Oncology,Buffalo, NY, USA 2Roswell Park Cancer Institute,Department Of Biostatistics And Bioinformatics,Buffalo, NY, USA
Introduction: Bone morphogenetic proteins (BMPs) are members of the TGFβ family of signaling pathways and are known to be essential in fetal development, tissue differentiation and a multitude of cellular functions. In breast cancer, differential expressions are noted among different subtypes. BMPs are also known to regulate the epithelial to mesenchymal transition, tissue invasion and metastasis. Low expression of BMP7 is known to be associated with a more metastatic phenotype, especially bone metastases. However, the impact of comprehensive BMPs gene expressions on breast cancer patients’ survival is still understudied. This study aimed to investigate the association of BMPs gene expression with breast cancer patients’ survival using a ‘big data’ approach employing RNA sequencing from The Cancer Genome Atlas (TCGA).
Methods: A total of 1093 treatment naïve breast cancers underwent genetic sequencing and the results of their sequencing stored in TCGA dataset. Overall survival (OS) was compared between high and low mRNA expression of indicated BMP related genes; BMP1, BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP10, BMP15 and BMP receptors 1A (BMPR1A) and 1B (BMPR1B), based upon RNA-sequencing data of TCGA.
Results: TCGA cohort was representative of national breast cancer patients with respect to stage, pathology and survival. High expression of BMP1 (p<0.001), BMP3 (p=0.002), BMP5 (p=0.020), BMP7 (p<0.001) and BMPR1A (p<0.001) significantly associated with better OS. On the other hand, high expression of BMP6 (p<0.001) and BMPR1B (p=0.005) significantly associated with worse OS. BMP2, BMP4, BMP10 and BMP15 did not associate with OS. When we analyzed by subtype, in consistent with the whole cohort analysis result, BMP7 high expression significantly associated with better prognosis in both ER positive (p<0.001) and negative tumors (p<0.001). Interestingly high expression of BMP6 associated with better prognosis in ER positive tumor (p=0.004), whereas it associated with worse prognosis in ER negative tumors (p=0.006).
Conclusion: BMP expression profiles may be of value in prognostication. Intervention in this pathway may serve to improve outcomes, manage metastatic disease and assist in clinical decision making on optimal therapy based on risk of recurrence or metastasis.