High lipocalin- 2 expression increases pemetrexed sensitivity in patients with lung adenocarcinoma

Abstract

Introduction: The aim of this study is to determine the expression level of lipocalin-2 protein in human lung adenocarcinom tissues and to evaluate the relationship between its expression levels and clinicopathological parameters, including response to pemetrexed, degree of tumor differentiation, driver mutation status, progression free survival (PFS) and overall survival (OS). Materials and methods: We retrospectively examined paraffin-embedded tissue sections from 30 metastatic lung adenocarcinoma patients whose clinical outcomes had been tracked after pemetrexed treatment. The expression status of Lipocalin-2 was determine by immunohistochemistry (IHC) using the anti-lipocalin-2 antibody. Results: Lipocalin-2 was highly expressed in 56% of the examined tumor tissues. There was significant association betwen high lipocalin-2 expression and increased pemetrexed sensitivity (p=0,028). There was no correlation between the degree of tumor differentiation and the level of lipocalin-2 expression. All five patient with EGFR mutation showed high lipocalin-2 expression (p=0,043). Kaplan-Meier survival analysis showed a significant correlation between expression levels of lipocalin-2 and PFS (p=0.014). Whereas there was no significant correlation betwen level of lipocalin-2 and OS although patients with high levels of this protein had a marginally longer survival time compared to those with low levels. Conclusion: Our data suggest that lipocalin-2 may be a predictive marker for pemetrexed effectiveness in patients with lung adenocarcinoma.