High expression of bone morphogenetic protein (BMP) 6 and BMP7 are associated with higher immune cell infiltration and better survival in estrogen receptor‑positive breast cancer

Katsuta,Eriko; Maawy,Ali   A.; Yan,Li; Takabe,Kazuaki

doi:10.3892/or.2019.7275

High expression of bone morphogenetic protein (BMP) 6 and BMP7 are associated with higher immune cell infiltration and better survival in estrogen receptor‑positive breast cancer

Authors:
- Eriko Katsuta
- Ali A. Maawy
- Li Yan
- Kazuaki Takabe
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Affiliations: Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA, Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
Published online on: August 12, 2019 https://doi.org/10.3892/or.2019.7275
Pages: 1413-1421
Copyright: © Katsuta et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

There are conflicted experimental results on the role of bone morphogenetic proteins (BMPs) in cancer. Some results suggest that BMPs act as tumor suppressors while other findings indicate that BMPs are oncogenic factors. In the present study, we aimed to investigate the association of BMP expression and the survival of breast cancer patients utilizing The Cancer Genome Atlas (TCGA). High expression levels of BMP1 (P<0.001), BMP3 (P=0.002), BMP5 (P=0.002), BMP7 (P<0.001) and BMPR1A (P<0.001) were associated with better overall survival (OS). On the other hand, high expression levels of BMP6 (P<0.001), BMP8A (P=0.031), BMP8B (P<0.001) and BMPR1B (P=0.005) were associated with worse OS. Most of the BMPs demonstrated differential expression levels between normal and tumor tissues. High expression of BMP7 was found to be significantly associated with better prognosis in both estrogen receptor (ER)‑positive (ER+) (P<0.001) and ER‑negative (ER‑) tumors (P<0.001), whereas high expression of BMP6 was associated with better prognosis only in ER+ tumors (P=0.004); it was associated with worse prognosis in ER‑ tumors (P=0.006). In the ER+ tumors, high expression of BMP7 as well as BMP6 were associated with higher infiltration of anticancer immune cells and cytolytic activity. These results suggest that high expression levels of BMP7 as well as BMP6 possess higher anticancer immunity which results in better prognosis in ER+ breast cancer. In conclusion, BMP expression profiles may be useful for prognostication. Intervention in this pathway may serve to improve outcomes, manage metastatic disease and assist in clinical decision making on optimal therapy based on the risk of recurrence or metastasis.

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