Prognostic Significance of Activated Leukocyte Cell Adhesion Molecule (ALCAM) in Association with Promoter Methylation of the ALCAM Gene in Breast Cancer

Molecules. 2018 Jan 9;23(1):131. doi: 10.3390/molecules23010131.

Abstract

Activated leukocyte cell adhesion molecule (ALCAM) has been implicated in tumorigenesis. In this study, we studied DNA methylation status of the ALCAM gene using pyrosequencing in breast cancer tissues. We analyzed the association between the methylation status of the ALCAM gene and its expression. Also, the effects of inflammation on the ALCAM gene methylation and its expression were investigated. The ALCAM gene methylation was associated with the ALCAM transcripts in tumor tissues. The methylation status of the ALCAM gene was not significantly different between tumor and normal tissues. The level of ALCAM transcripts was associated with the expression of TNFα, NF-κB p50, IL-4, and intratumoral inflammation. The IHC expression of ALCAM was associated with histologic grade, HER2 overexpression and molecular subtype. The expression of TNFα, NF-κB p50, and IL-4 showed significant association with the clinicopathologic characteristics. In conclusion, the ALCAM gene methylation was related to the level of ALCAM transcripts. Also, the level of ALCAM transcripts was associated with the inflammatory markers in breast cancer. Our results suggest that the methylation of the ALCAM gene contributes to the decreased expression of ALCAM. Also, ALCAM is linked to the inflammatory response in breast cancer.

Keywords: activated leukocyte cell adhesion molecule; breast cancer; epigenetics; inflammation; methylation.

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule / genetics
  • Activated-Leukocyte Cell Adhesion Molecule / metabolism*
  • Aged
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / metabolism
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Computational Biology / methods
  • DNA Methylation*
  • Female
  • Fetal Proteins / genetics*
  • Fetal Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-4 / metabolism
  • Middle Aged
  • NF-kappa B / metabolism
  • Prognosis
  • Promoter Regions, Genetic*

Substances

  • ALCAM protein, human
  • Activated-Leukocyte Cell Adhesion Molecule
  • Antigens, CD
  • Biomarkers, Tumor
  • Cell Adhesion Molecules, Neuronal
  • Fetal Proteins
  • NF-kappa B
  • Interleukin-4