Neutrophil Gelatinase-associated Lipocalin as a Theragnostic Marker in Perihilar Cholangiocarcinoma

Anticancer Res. 2018 Dec;38(12):6737-6744. doi: 10.21873/anticanres.13043.

Abstract

Background/aim: Platforms using valid molecular targets can provide concurrent diagnostic and treatment (theragnostic) options in perihilar cholangiocarcinoma (PHC). Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker in the biliary secretome of PHC. Its potential as a theragnostic target and its prognostic significance in this cancer was, therefore, explored.

Materials and methods: In-vitro studies were used to determine NGAL localization in several cholangiocarcinoma cell lines. Tissue expression of NGAL was quantified in PHC resection cases from 2000-2010 by immunohistochemistry.

Results: NGAL was expressed in the majority of tested cell lines and localized to their membranes. Tissues from 54 patients underwent NGAL immunohistochemistry. Median tumoral NGAL expression was significantly higher than that in matched liver controls (p<0.001). Higher NGAL tumor expression was associated with nodal metastasis (p=0.021), although no significant association with survival was observed.

Conclusion: The expression and localization of NGAL in PHC make it a valid candidate biomarker for exploitation in theragnostic platforms.

Keywords: Klatskin tumor; Perihilar cholangiocarcinoma; bile duct cancer; matrix metalloproteinase-9; molecular targeting; neutrophil gelatinase associated lipocalin.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms / diagnosis*
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology
  • Biomarkers, Tumor* / metabolism
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunohistochemistry
  • Klatskin Tumor / diagnosis*
  • Klatskin Tumor / metabolism
  • Klatskin Tumor / pathology
  • Lipocalin-2 / physiology*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Prognosis

Substances

  • Biomarkers, Tumor
  • LCN2 protein, human
  • Lipocalin-2