Introduction We have previously demonstrated that the level of neutrophil gelatinase-associated lipocalin (NGAL) is increased in the bile of patients with pancreatobiliary malignancy. NGAL is expressed by activated neutrophils and many other cell types and is thought to have bacteriostatic, pro-proliferative and pro-metastatic functions. NGAL can be detected in the blood plasma. We hypothesised that the plasma NGAL level is elevated in patients with cholangiocarcinoma (CC) compared with patients with primary sclerosing cholangitis (PSC), and with healthy volunteers.
Methods Plasma samples were collected from 97 patients with confirmed CC, 62 patients with PSC and no CC and 82 healthy controls. Plasma NGAL quantification was performed in duplicate on plasma from each subject using a Quantikine ELISA kit (R&D Systems, Minneapolis, Minnesota, USA). CC and healthy control cohorts were compared using the Student t test and receiver operator characteristic (ROC) analysis. Differences between CC and PSC cohorts were then sought. Pearson's correlation analysis was used to assess relationships between the levels of NGAL and other plasma markers.
Results Median NGAL concentrations (range) in CC, PSC and healthy controls were 92 ng/ml (14–644), 83 (43–171) and 64 (29–132) respectively. NGAL levels were significantly higher in plasma from CC patients compared with healthy controls (p<0.0001). The area under the ROC curve was 0.71 (95% CI 0.64 to 0.79 p<0.0001). NGAL levels were significantly higher in plasma samples from the CC cohort than those from the PSC cohort (p<0.01) with a ROC-AUC of 0.57 (95% CI 0.48 to 0.65 p<0.167). There was no relationship between NGAL levels and CRP (r2=0.14), white cell count (r2=0.09), bilirubin (r2=0.01), ALP (r2=0.02) or creatinine (r2=0.03). There was moderate correlation between NGAL and Ca19-9 concentrations (r2=0.38).
Conclusion NGAL is expressed at significantly higher concentrations in the plasma of patients with CC compared to plasma from healthy controls and from subjects with PSC. This finding appears to be independent of renal impairment, cholestasis or systemic inflammatory response, suggesting that NGAL may represent a novel plasma biomarker of CC.
Competing interests None declared.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.