Protein and mRNA expression of notch pathway components in operable tumors of patients with laryngeal cancer

Anticancer Res. 2014 Nov;34(11):6495-503.

Abstract

Background: There exist substantial evidence that laryngeal cancer represents a unique entity among squamous head and neck carcinomas.

Materials and methods: Tumors from 289 patients with squamous cell laryngeal cancer were assessed for protein (immunohistochemistry) and mRNA (qRT-PCR) expression of Notch pathway components (Notch1 to 4 receptors and Jagged1 ligand) on tissue microarrays.

Results: In univariate analysis, enhanced nuclear Jagged1 expression conferred a longer disease-free survival (DFS) (p=0.013) and overall survival (OS) (p=0.004), in contrast to the unfavorable prognostic value of Notch3 for both DFS (p=0.009) and OS (p=0.024). In multivariate analysis, overexpression of either Notch or cytoplasmic Jagged1 conferred an unfavorable effect on DFS (Hazard Ratio=1.88, 95% Confidence Interval=1.03-3.43, p=0.04).

Conclusion: Our study indicates a consistent unfavorable effect of Notch3 and cytoplasmic Jagged1 protein expression, a favorable impact of nuclear Jagged 1 localization, and a differential prognostic value of Notch2 expression according to the presence of cytoplasmic Jagged 1.

Keywords: Jagged1; Laryngeal cancer; Notch; immunohistochemistry; mRNA expression; multivariate analysis; prognostic value.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / metabolism*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / surgery
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Jagged-1 Protein
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / mortality
  • Laryngeal Neoplasms / surgery
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, Notch / genetics*
  • Receptors, Notch / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serrate-Jagged Proteins
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Notch
  • Serrate-Jagged Proteins