Increased cytoplasmic expression of DLL4 is associated with favorable prognosis in colorectal cancer

Future Oncol. 2021 Aug;17(24):3231-3242. doi: 10.2217/fon-2020-0840. Epub 2021 Jun 22.

Abstract

Aims: DLL4 of the Notch pathway is a key regulator of VEGF expression, which mediates tumor neovascularization and stem cell self-renewal in colorectal cancer (CRC). The authors investigated the association of DLL4 expression with the clinicopathological characteristics and survival outcomes of CRC patients. Methods: DLL4 expression level was evaluated in 199 CRC samples using immunohistochemistry analysis of tissue microarrays. Results: The high expression of DLL4 was inversely associated with distant metastasis (p < 0.029), tumor recurrence (p < 0.04) and longer overall survival following curative surgery compared with those with low DLL4 expression with 95% CI (log-rank test: p = 0.050). In univariate analysis, histological grade (hazard ratio: 3.859; 95% CI: 1.081-13.784; p = 0.038) was a strong prognostic risk factor, affecting the overall survival of CRC patients. Conclusion: The authors' results demonstrate that DLL4 expression might be considered a favorable prognostic factor for overall survival in CRC patients.

Keywords: DLL4; colorectal cancer; distant metastasis; overall survival; tissue microarray; tumor recurrence.

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis*
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Calcium-Binding Proteins / biosynthesis*
  • Colorectal Neoplasms / pathology*
  • Cytoplasm / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • DLL4 protein, human