Can NGAL be employed as prognostic and diagnostic biomarker in human cancers? A systematic review of current evidence

Background: Some studies have reported differentially altered neutrophil gelatinase-associated lipocalin (NGAL) levels in several malignancies. We evaluated NGAL measured in plasma or urine as both prognostic and diagnostic marker for different types of human tumors. Methods: We performed systematic electronic searches in Medline, Embase and CRDTAS. Studies were included if they evaluated NGAL as a prognostic or diagnostic marker for human cancers. The selection of the studies, screening of the full texts and data extraction were conducted independently by 2 authors. We used the random-effects model for the meta-analyses. A methodological assessment was completed. Results: We included 35 studies dedicated to colorectal, pancreas, breast, thyroid, gastric, kidney, endometrial, brain, liver, lung, esophageal, oral and ovarian cancers. Our meta-analyses showed that, in patients with colorectal and breast cancer, positive NGAL expression was associated with a decrease of disease-free survival (hazard ratio [HR] = 2.27, 95% confidence interval [95% CI], 1.54-3.36; HR = 1.78, 95% CI, 1.33-2.38, respectively). NGAL was a negative prognostic marker of overall survival in colorectal (HR = 2.37, 95% CI, 1.68-3.34) and endometrial (HR = 4.38, 95% CI, 1.9-10.12) cancers. Discriminative power of NGAL between cancer patients and control was moderate in colorectal cancer (area under the curve [AUC] = 0.6; pooled sensitivity 0.56; pooled specificity 0.72), acceptable in pancreatic cancer (AUC = 0.8; pooled sensitivity 0.6; pooled specificity 0.8) and good in thyroid cancer (AUC = 0.9; pooled sensitivity 0.85; pooled specificity 0.96). Conclusions: NGAL determination in plasma and urine could be useful in the prognosis of colorectal and breast cancer, but its prognostic accuracy remains uncertain for other human tumors.