Abstract
BackgroundAlthough 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.MethodsPreoperative 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.ResultsThe 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).ConclusionsOur 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.
Highlights
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
We examined the association between preoperative serum levels of lipocalin-2 and MMP-9 and disease-free survival (DFS) and determined the potential of both proteins as noninvasive biomarkers in predicting the recurrence of breast cancer
In the present study, we found that patients with elevated lipocalin-2 or MMP-9 levels at diagnosis had poorer DFS than patients with low lipocalin-2 or MMP-9 levels
Summary
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. Considering the substantial increase in breast cancer survivors, to identify prognostic factors associated with recurrence and survival is more important today ever than before after primary treatment. Known only as an antibacterial factor of innate immunity, lipocalin-2 has been suggested to participate in diverse biological processes such as, inflammation, acute organ damage, lipid metabolism, and cancer development. The mechanisms are not clearly elucidated, several studies suggest possible mechanisms underlying the role of lipocalin-2 in mammary tumor initiation and progression [6]
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