Clinic implication of MUC1 O-glycosylation and C1GALT1 in esophagus squamous cell carcinoma

Sci China Life Sci. 2018 Nov;61(11):1389-1395. doi: 10.1007/s11427-017-9345-7. Epub 2018 Aug 1.

Abstract

Esophagus squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors in the world. Our previous data demonstrates that oncoprotein MUC1 is related with metastasis and poor outcome of ESCC. However, alteration of MUC1 in ESCC remains unclear. Using ONCOMINE and COSMIC databases, we analyzed MUC1 gene copy numbers and gene mutations and found that MUC1 had high expression level but few gene mutations in ESCC. Further study of ESCC samples indicated that MUC1 O-glycosylation levels were higher in tumor tissues than that in para-carcinoma tissues in 10 of 14 pairs of ESCC samples. Moreover, we verified a potential link between MUC1 O-glycosylation and C1GALT1, which was further supported by IHC analysis on 38 ESCC and 19 para-carcinoma samples. More importantly, co-expression of MUC1 Oglycosylation and C1GALT1 presented positive correlations with both lymph node metastasis and survival time of ESCC patients. Our work collectively indicates that C1GALT1 is associated with O-glycosylated MUC1 in ESCC, not only suggesting a diagnostic significance of C1GALT1 and MUC1 O-glycosylation in ESCC, but also opening novel insights into targeting C1GALT1 and MUC1 O-glycosylation to suppress ESCC cells metastasis in patients.

Keywords: CIGALT1; ESCC; MUC1; gene mutation; glycosylation.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Databases, Genetic
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Galactosyltransferases / genetics*
  • Gene Expression
  • Genetic Association Studies
  • Glycosylation
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Mucin-1 / genetics*
  • Mucin-1 / metabolism*
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • MUC1 protein, human
  • Mucin-1
  • C1GALT1 protein, human
  • Galactosyltransferases