The BMP inhibitor DAND5 in serum predicts poor survival in breast cancer
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Yayun Chi1,*, Ling Yao1,*, Xin Hu1,*, Sheng Huang1, Naisi Huang1, Shan Li1, Zhiming Shao1, Jiong Wu2
1Department of Breast Surgery, Breast Cancer Institute, Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
2Department of Breast Surgery, Breast Cancer Institute, Shanghai Cancer Center, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
*These authors have contributed equally to this work
Jiong Wu, e-mail: [email protected]
Zhiming Shao, e-mail: [email protected]
Keywords: DAND5, breast cancer, biomarker, secreted factor, prognosis
Received: July 28, 2015 Accepted: January 29, 2016 Published: February 19, 2016
Background & Aims: Breast cancer (BC) is prevalent worldwide malignant cancer. Improvements in timely and effective diagnosis and prediction are needed. As reported, secreted DAND5 is contributed to BC metastasis. We aim to assess whether DAND5 in peripheral blood serum could determine BC-specific mortality.
Methods: We used immunohistochemistry staining to detect DAND5 expression in our BC tissue array including 250 samples. Angiogenesis assay and xenograft mice model were used to examine the secreted DAND5 function in BC progression. Serum concentration of DAND5 was examined by ELISA in 1730 BC patients. Kaplan-Meier and adjusted Cox proportional hazards models were utilized to analyze the prognosis and survival of BC patients.
Results: Tissue array results showed that positive DAND5 staining cases displayed a higher likelihood of occurrence of disease events (HR=5.494; 95% CI: 1.008-2.353; P=0.048) in univariate analysis and remained the same trend in multivariate analysis (HR=2.537; 95% CI: 1.056-6.096; P=0.037). DAND5 positive patients exerted generally poor DFS (P=0.041) in the Kaplan-Meier survival analysis. Furthermore, secreted DAND5 promoted tumor growth and angiogenesis in vitro and in vivo. In addition, positive DAND5 in BC patients serum was associated with increased risk of disease events occurrence (univariate: HR=1.58; 95% CI: 1.206-2.070; P=0.001; multivariate: HR=1.4; 95% CI: 1.003-1.954; P=0.048) in univariate and multivariate survival analysis. In the Kaplan-Meier analysis, serum DAND5 positively correlated with poor DFS (P=0.001) and DDFS (P=0.002).
Conclusions: DAND5 was correlated with poor survival and could serve as an easily detectable serum biomarker to predict the survival of breast cancer.
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