Immunohistochemical expression of Notch1, Jagged1, NF-κB and MMP-9 in colorectal cancer patients and the relationship to clinicopathological parameters

Cancer Biomark. 2015;15(6):889-97. doi: 10.3233/CBM-150533.

Abstract

Background: Activation of Notch and NF-κB signaling has been frequently observed in colorectal cancer (CRC) patients and contributes to the chemo-resistance and treatment failure. However, the relationship between these signaling pathways and CRC has not been clearly described.

Objective: To investigate the expression of Notch1, Jagged1, NF-κB and MMP-9 in CRC patients and analyze their correlation with clinicopathological factors.

Methods: Expression of Notch1, Jagged1, NF-κB and MMP-9 was visualized by immune-histology in the tumor tissue, adjacent and distant normal tissues from 47 CRC patients without receiving chemotherapy or radiotherapy.

Results: Notch1 (80.8%), Jagged1 (80.8%), NF-κB (70.2%) and MMP-9 (76.6%) were overexpressed in cancer tissues compared normal tissues (P< 0.05). The intensity of Notch1, Jagged1 and NF-κB expression was associated with histological grading, depth of invasion, TNM staging and lymph node metastasis of CRC. MMP-9 was intimately correlated with depth of invasion, TNM staging and lymph node metastasis. NF-κB, MMP-9 and Notch1 expression was positively correlated (P< 0.05), and the same positive correlation was found among NF-κB, MMP-9 and Jagged1 expression (P< 0.05).

Conclusion: Notch1, Jagged1, NF-κB and MMP-9 probably play a pivotal role during the CRC development, serving as biomarkers for early detection of the recurrence and metastasis and prognosis of CRC.

Keywords: Colorectal cancer; MMP-9; NF-κB; jagged; notch.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Jagged-1 Protein
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Membrane Proteins / metabolism*
  • Middle Aged
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Staging
  • Prognosis
  • Receptor, Notch1 / metabolism*
  • Serrate-Jagged Proteins
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • NF-kappa B
  • NOTCH1 protein, human
  • Receptor, Notch1
  • Serrate-Jagged Proteins
  • MMP9 protein, human
  • Matrix Metalloproteinase 9