Up-regulation of Neutrophil Gelatinase-Associated Lipocalin in Colorectal Cancer Predicts Poor Patient Survival

Background

Lipocalin-2 (Lcn-2) is expressed in human neutrophils and epithelial cells, particularly in the presence of inflammation or cancer. It was shown to be highly expressed in various human cancers. Increased protein levels were associated with decreased survival of patients with breast or gastric cancer. The main focus of this work was to analyze the implication of Lcn-2 up-regulation in the genesis of colon cancer.

Methods

Expression of Lcn-2 was analyzed in colorectal carcinoma cell lines, paired colorectal carcinoma tissues, and regular mucosa by Western blot analysis. Lcn-2 immunohistochemical staining was performed in 192 colorectal carcinoma resection specimens and correlated with clinicopathologic parameters.

Results

Western blot analysis of colorectal carcinoma tissues demonstrated Lcn-2 overexpression in carcinomas as compared with regular mucosa. Immunohistochemical staining revealed Lcn-2 expression in 179 (93.2 %) colorectal carcinoma tissues. Intense immunoreactivity was significantly correlated with metastasis (p = 0.042) and UICC stage (p = 0.027). Survival analysis according to the Kaplan–Meier method revealed a significant association between Lcn-2 overexpressing tumors and overall survival (p < 0.001) and disease-free survival (p < 0.001).

Conclusions

Our data provide evidence that Lcn-2 expression is up-regulated with tumor progression and was found to be a predictor of overall survival.