title: Can NGAL be employed as prognostic and diagnostic biomarker in human cancers? A systematic review of current evidence.
abstract: 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.
authors.affiliation: Laboratory of Endocrinology, Department of Laboratory Medicine and Pathological Anatomy, Azienda USL of Modena, Modena - Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Roli
authors.affiliation: Laboratory of Toxicology, Department of Laboratory Medicine and Pathological Anatomy, Azienda USL of Modena, Modena - Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pecoraro
authors.affiliation: Laboratory of Toxicology, Department of Laboratory Medicine and Pathological Anatomy, Azienda USL of Modena, Modena - Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Trenti
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D000071068:Lipocalin-2 / Q000378:metabolism*; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C489506:LCN2 protein, human; D000071068:Lipocalin-2