Expression, Function, and Prognostic Value of MAGE-D4 Protein in Esophageal Squamous Cell Carcinoma

Anticancer Res. 2019 Nov;39(11):6015-6023. doi: 10.21873/anticanres.13807.

Abstract

Background/aim: We previously reported that expression of melanoma-associated antigen (MAGE)-D4 mRNA was a prognostic factor for esophageal squamous cell carcinoma (ESCC). The aim of this study was to validate the expression of MAGE-D4 in two additional patient cohorts, and to investigate its biological functions.

Materials and methods: The role of MAGE-D4 in cell proliferation, adhesion, and migration was determined by gene knockdown experiments in the KYSE590 cell line. MAGE-D4 protein expression was analyzed in ESCC tissues by immunohistochemistry. A second validation cohort consisted of an ESCC mRNA dataset from The Cancer Genome Atlas.

Results: Knockdown of MAGE-D4 significantly decreased cell proliferation and migration. Expression of MAGE-D4 protein was significantly associated with disease-free survival. In the second validation cohort, high MAGE-D4 mRNA expression was associated with significantly shorter overall survival and disease-free survival.

Conclusion: MAGE-D4 plays an important role in the malignant behavior of ESCC. MAGE-D4 was validated as a prognostic indicator in two independent ESCC patient cohorts.

Keywords: Esophageal cancer; MAGE-D4; biomarker.

MeSH terms

  • Aged
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Adhesion
  • Cell Proliferation
  • Cohort Studies
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / surgery
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / secondary*
  • Esophageal Squamous Cell Carcinoma / surgery
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • RNA, Small Interfering / genetics
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • MAGED1 protein, human
  • Neoplasm Proteins
  • RNA, Small Interfering