Open Access Research article

The association between the preoperative serum levels of lipocalin-2 and matrix metalloproteinase-9 (MMP-9) and prognosis of breast cancer

Hyuna Sung1, Ji-Yeob Choi16, Sang-Ah Lee2, Kyoung-Mu Lee3, Sohee Han4, Sujee Jeon5, Minkyo Song4, Yunhee Lee1, Sue K Park146, Keun-Young Yoo4, Dong-Young Noh67, Sei-Hyun Ahn8 and Daehee Kang146*

Author Affiliations

1 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea

2 Department of Preventive Medicine, Kangwon National University School of Medicine, Kangwon, Korea

3 Department of Environmental Health, Korea National Open University, Seoul, Korea

4 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea

5 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Korea

6 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

7 Department of Surgery, Seoul National University College of Medicine, Seoul, Korea

8 Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea

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BMC Cancer 2012, 12:193  doi:10.1186/1471-2407-12-193

Published: 28 May 2012

Abstract

Background

Although a number of experimental studies have suggested the role of lipocalin-2 (LCN2) and matrix metalloproteinase-9 (MMP-9) in breast cancer progression, limited numbers of epidemiological studies have examined the relationship between the levels of lipocalin-2 and MMP-9 and breast cancer survival.

Methods

Preoperative serum levels of lipocalin-2 and MMP-9 were measured in 303 breast cancer patients and 74 healthy controls recruited between 2004 and 2007. We examined the association between lipocalin-2 and MMP-9 levels and disease-free survival (DFS) using Cox proportional hazard regression model.

Results

The serum levels of lipocalin-2 and MMP-9 were not significantly different between patients and controls (P > 0.05). Elevated lipocalin-2 and MMP-9 levels were associated with reduced DFS of breast cancer ( Ptrend = 0.029 and Ptrend = 0.063, respectively). When lipocalin-2 and MMP-9 levels were categorized based on the combined risk score, patients with higher levels of both lipocalin-2 and MMP-9 exhibited poor DFS compared to patients with lower levels (Ptrend = 0.004). Furthermore, these effects were profound in patients with BMI less than 25 kg/m2 (adjusted hazard ratio (aHR), 3.17; 95% confidence intervals (CI), 1.66-6.06, Ptrend < 0.001) or lymph-node negative breast cancer (aHR, 5.36; 95% CI, 2.18-13.2, Ptrend < 0.001).

Conclusions

Our study suggests that the elevated levels of lipocalin-2 and MMP-9 are associated with reduced breast cancer survival, particularly in patients with lower BMI and lymph-node negative breast cancers.