Jagged1 and DLL4 expressions in benign and malignant pancreatic lesions and their clinicopathological significance

Hepatobiliary Pancreat Dis Int. 2016 Dec;15(6):640-646. doi: 10.1016/s1499-3872(16)60110-8.


Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis. Despite intensive research, markers for the early diagnosis, prognosis, and targeting therapy of PDAC are not available. This study aimed to investigate the protein expressions of Jagged1 and DLL4 in PDAC tumor, benign pancreatic and normal pancreatic tissues, and analyze the associations of the two proteins with the clinical and pathological characteristics of PDAC.

Methods: A total of 106 PDAC tumor tissues and 35 peritumoral tissues were collected from January 2000 to December 2011 at our hospitals. Thirteen normal pancreatic tissues and 55 benign pancreatic specimens were collected at the same period. Immunohistochemical staining was used to measure Jagged1 and DLL4 protein expressions in these tissues.

Results: The percentage of positive Jagged1 and DLL4 was significantly higher in PDAC than in normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P<0.01). The higher Jagged1 and DLL4 expressions in PDAC were significantly associated with poor differentiation, maximum tumor size >5 cm, invasion, regional lymph node metastasis, and TNM III/IV disease (P<0.05). In PDAC, Jagged1 expression positively correlated with DLL4 expression. Univariate Kaplan-Meier analysis showed that positive Jagged1 and DLL4 expressions were significantly associated with shorter survival in patients with PDAC. Multivariate Cox regression analysis showed that positive Jagged1 and DLL4 expressions were independent prognostic factors for poor prognosis of patients with PDAC.

Conclusion: Positive Jagged1 and DLL4 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in patients with PDAC.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Biomarkers, Tumor / analysis*
  • Calcium-Binding Proteins
  • Carcinoma, Pancreatic Ductal / chemistry*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Case-Control Studies
  • Chi-Square Distribution
  • Female
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / analysis*
  • Jagged-1 Protein / analysis*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Pancreatic Neoplasms / chemistry*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Risk Factors
  • Time Factors
  • Up-Regulation


  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • DLL4 protein, human
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein