title: NGAL expression is elevated in both colorectal adenoma-carcinoma sequence and cancer progression and enhances tumorigenesis in xenograft mouse models.
abstract: OBJECTIVE
  There is growing evidence implicating that neutrophil gelatinase-associated lipocalin (NGAL) plays a role in the development and progression of cancers. However, the effect of NGAL in colorectal carcinoma (CRC) has not been clearly elucidated. In this study, we investigated the role of NGAL in the tumorigenesis and progression of CRC and evaluated the clinical value of NGAL expression.
  
  
  METHODS
  We examined NGAL expression in 526 colorectal tissue samples, including 53 sets of matched specimens (histologically normal mucosa, adenomas, and carcinomas) using immunohistochemical analysis. In CRCs, correlations between NGAL expression and clinicopathologic parameters were analyzed, and survival analysis was conducted. The role of NGAL was further tested using mouse xenograft models.
  
  
  RESULTS
  NGAL expression was elevated during the colorectal adenoma-carcinoma sequence both among the 526 cases (r(s) = 0.66, P < 0.001) and in the 53 sets of matched specimens (r(s) = 0.60, P < 0.001). In CRCs, NGAL expression was associated with cancer stage (P = 0.041) and tumor recurrence in stage II patients (P = 0.037). Survival analysis revealed that NGAL expression was an independent prognostic factor for overall survival (HR = 1.84, P = 0.004) and for disease-free survival of stage II patients (HR = 5.88, P = 0.021). In mouse models, the xenografts in cecum and spleen were heavier and more numerous in the group injected with NGAL-overexpressing CRC cells (P < 0.05).
  
  
  CONCLUSIONS
  NGAL overexpression may promote the tumorigenesis and progression of CRC. Detecting NGAL expression in tumor tissues may be useful for evaluating prognosis of patients with CRC.
authors.affiliation: Department of Pathology and Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokoi
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Limei
authors.initials: L
authors.lastname: Hu
authors.forename: Ben
authors.initials: B
authors.lastname: Liu
authors.forename: Kexin
authors.initials: K
authors.lastname: Chen
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: Dominic
authors.initials: D
authors.lastname: Fan
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics* / Q000378:metabolism*; D000236:Adenoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics* / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D012008:Recurrence; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins