Abstract

Background & AimsBreast 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.MethodsWe 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.ResultsTissue 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).ConclusionsDAND5 was correlated with poor survival and could serve as an easily detectable serum biomarker to predict the survival of breast cancer.

Highlights

  • Breast cancer is the most common malignancy among women and represents an important worldwide public health issue [1, 2]

  • Tissue array results showed that positive DAND5 staining cases displayed a higher likelihood of occurrence of disease events (HR=5.494; 95% confidence interval (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)

  • Positive DAND5 in Breast cancer (BC) patients serum was associated with increased risk of disease events occurrence in univariate and multivariate survival analysis

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Summary

Introduction

Breast cancer is the most common malignancy among women and represents an important worldwide public health issue [1, 2]. It is the major cause of cancerrelated death in women and treatment is difficult in patients with tumor metastasis [3]. Many other secreted factors are used in other tumors, including AFP (α-fetoprotein), CEA (carcinoembryonic antigen) and PSA (prostate-specific antigen). They are all secreted by cancer cells through cellular membranes or exosomes and can be detected in the patients’ body fluid. We aim to assess whether DAND5 in peripheral blood serum could determine BC-specific mortality

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