Early diagnosis of pancreatic cancer: Neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia

N. Moniaux, S. Chakraborty, M. Yalniz, J. Gonzalez, V. K. Shostrom, J. Standop, Subodh M Lele, Michel M Ouellette, P. M. Pour, A. R. Sasson, R. E. Brand, Michael A Hollingsworth, Maneesh Jain, Surinder Kumar Batra

Research output: Contribution to journalArticle

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Abstract

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic intraepithelial neoplasia, premalignant lesions preceding invasive cancer. To examine a possible correlation between NGAL expression and the degree of differentiation, we also analysed NGAL levels in pancreatic cancer cell lines with varying grades of differentiation. Although NGAL expression was strongly upregulated in pancreatic cancer, and moderately in pancreatitis, only a weak expression could be detected in the healthy pancreas. The average composite score for adenocarcinoma (4.26±2.44) was significantly higher than that for the normal pancreas (1.0) or pancreatitis (1.0) (P<0.0001). Further, although both well- and moderately differentiated pancreatic cancer were positive for NGAL, poorly differentiated adenocarcinoma was uniformly negative. Importantly, NGAL expression was detected as early as the PanIN-1 stage, suggesting that it could be a marker of the earliest premalignant changes in the pancreas. Further, we examined NGAL levels in serum samples. Serum NGAL levels were above the cutoff for healthy individuals in 94% of pancreatic cancer and 62.5% each of acute and chronic pancreatitis samples. However, the difference between NGAL levels in pancreatitis and pancreatic cancer was not significant. A ROC curve analysis revealed that ELISA for NGAL is fairly accurate in distinguishing pancreatic cancer from non-cancer cases (area under curve=0.75). In conclusion, NGAL is highly expressed in early dysplastic lesions in the pancreas, suggesting a possible role as an early diagnostic marker for pancreatic cancer. Further, serum NGAL measurement could be investigated as a possible biomarker in pancreatitis and pancreatic adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)1540-1547
Number of pages8
JournalBritish journal of cancer
Volume98
Issue number9
DOIs
StatePublished - May 6 2008

Fingerprint

Pancreatic Neoplasms
Early Detection of Cancer
Neoplasms
Pancreatitis
Pancreas
Adenocarcinoma
Biomarkers
Lipocalin-2
ROC Curve
Serum
Chronic Pancreatitis
Microarray Analysis
Area Under Curve
Glycoproteins
Enzyme-Linked Immunosorbent Assay

Keywords

  • Diagnosis
  • Lipocalin
  • NGAL
  • PanIN
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Early diagnosis of pancreatic cancer : Neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia. / Moniaux, N.; Chakraborty, S.; Yalniz, M.; Gonzalez, J.; Shostrom, V. K.; Standop, J.; Lele, Subodh M; Ouellette, Michel M; Pour, P. M.; Sasson, A. R.; Brand, R. E.; Hollingsworth, Michael A; Jain, Maneesh; Batra, Surinder Kumar.

In: British journal of cancer, Vol. 98, No. 9, 06.05.2008, p. 1540-1547.

Research output: Contribution to journalArticle

Moniaux, N. ; Chakraborty, S. ; Yalniz, M. ; Gonzalez, J. ; Shostrom, V. K. ; Standop, J. ; Lele, Subodh M ; Ouellette, Michel M ; Pour, P. M. ; Sasson, A. R. ; Brand, R. E. ; Hollingsworth, Michael A ; Jain, Maneesh ; Batra, Surinder Kumar. / Early diagnosis of pancreatic cancer : Neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia. In: British journal of cancer. 2008 ; Vol. 98, No. 9. pp. 1540-1547.
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