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骨形态发生蛋白（骨形成蛋白，BMP）属于转化生长因子β超家族，是在骨基质中发现的一类糖蛋白，因其具有诱导异位骨形成的作用而得名。目前，已经有15个BMP被相继克隆。BMP的生物学作用不仅仅局限于促进新骨的形成，还在细胞生长、分化、迁移、凋亡以及胚胎和器官发生中发挥重要作用。近年来越来越多的研究表明，BMP的异常表达常常与肿瘤的发生和转移有关，在许多非骨源性肿瘤中均发现有BMP的过表达，如乳腺癌、前列腺癌和肺癌等。BMP与肿瘤的密切关系，使其在肿瘤治疗和预后方面具有重要价值。 BMP能够参与多种肿瘤的发生、发展和转移过程。BMP在不同类型肿瘤中往往发挥不同的作用，既可以抑制肿瘤生长，又可以促进肿瘤生长，还与肿瘤骨转移有关。由于BMP在肿瘤中的不同作用，在临床上可评价预后、治疗疾病和判断肿瘤发展阶段，具有广阔的应用前景。 Oncotarget. 2016 Feb 19. [Epub ahead of print] The BMP inhibitor DAND5 in serum predicts poor survival in breast cancer. Chi Y, Yao L, Hu X, Huang S, Huang N, Li S, Shao Z, Wu J. Department 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. 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. KEYWORDS: DAND5; biomarker; breast cancer; prognosis; secreted factor PMID: 26908452 DOI: 10.18632/oncotarget.7498
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