Demethylation-mediated upregulation of melanoma-associated antigen-A11 correlates with malignant progression of esophageal squamous cell carcinoma

Dig Liver Dis. 2019 Oct;51(10):1475-1482. doi: 10.1016/j.dld.2019.04.018. Epub 2019 May 31.

Abstract

Background: The expression and methylation status of oncogenes are closely related to the onset and progression of cancer.

Aims: To explore the role and methylation status of melanoma-associated antigen-A11 in the pathogenesis of esophageal squamous cell carcinoma.

Methods: 116 esophageal squamous cell carcinoma patients with tumor tissues and corresponding adjacent normal tissues were obtained. The expression level and methylation status of melanoma-associated antigen-A11 in esophageal cancer cell lines and esophageal squamous cell carcinoma tissues were determined respectively.

Results: Significant up-regulation of melanoma-associated antigen-A11 was detected in esophageal cancer cell lines and esophageal squamous cell carcinoma tissues. Up-regulation of melanoma-associated antigen-A11 contributed to proliferation and invasion in cancer cells. Hypomethylation of the CpG site was associated with pathological differentiation, clinical stage, tumor size, lymph node metastasis and distant metastasis. Esophageal squamous cell carcinoma patients in stage III and IV, with high expression of melanoma-associated antigen-A11 or hypomethylation of the CpG site within the promoter demonstrated poor survival.

Conclusion: Melanoma-associated antigen-A11 is up-regulated in esophageal squamous cell carcinoma at least partly by hypomethylation of the CpG site within the promoter and this hypomethylation may affect the prognosis of esophageal squamous cell carcinoma patients.

Keywords: ESCC; Expression; MAGE-A11; Methylation; Prognosis.

MeSH terms

  • Antigens, Neoplasm / metabolism*
  • Cell Line, Tumor
  • CpG Islands
  • DNA Methylation
  • Disease Progression
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / metabolism*
  • Esophageal Squamous Cell Carcinoma / mortality
  • Female
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Survival Analysis
  • Up-Regulation

Substances

  • Antigens, Neoplasm
  • MAGEA11 protein, human
  • Neoplasm Proteins