Low expression of polypeptide GalNAc N-acetylgalactosaminyl transferase-3 in lung adenocarcinoma: impact on poor prognosis and early recurrence

Br J Cancer. 2004 Jan 26;90(2):436-42. doi: 10.1038/sj.bjc.6601531.

Abstract

Initial glycosylation of mucin-type O-linked protein is catalysed by one of the UDP-GalNAc: polypeptide N-acetyl-galactosaminyl transferase-3 (GalNAc-T3). O-glycosylation is important in the binding of cell adhesion molecules, cell differentiation, invasion, and metastasis in tumours. This study was designed to detect GalNAc-T3 expression in lung adenocarcinoma by using immunohistochemical staining, and to evaluate the relationship between the GalNAc-T3 expression level and prognosis and recurrence in completely resected lung adenocarcinoma patients. A low expression of GalNAc-T3 was detected in the cytoplasm of tumour cells in 79 of 148 patients (53.4%) with lung adenocarcinoma. The low expression of GalNAc-T3 was associated with poorly differentiated tumour (P<0.0001), poor pathologic stage (P<0.0001), lymph node metastasis (P<0.0001), and tumour recurrence (P=0.016). The lung carcinoma patients with low GalNAc-T3 expression had a poorer prognosis than those with high GalNAc-T3 expression, using both univariate and multivariate analyses (overall survival: P<0.0001 and P=0.011, respectively). In addition, multivariate analysis of the clinicopathological characteristics of stage I lung adenocarcinoma indicated that the low expression of GalNAc-T3 was a significant independent factor for predicting poor prognosis and early recurrence (P=0.006, rr=2.87 and P=0.019, rr=3.05, respectively). The low expression of GalNAc-T3 may be a useful marker for predicting poor prognosis and early recurrence in completely resected lung carcinoma patients, particularly patients with stage I diseases.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Aged
  • Biomarkers, Tumor / analysis*
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cohort Studies
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • N-Acetylgalactosaminyltransferases / biosynthesis*
  • N-Acetylgalactosaminyltransferases / pharmacology
  • Neoplasm Proteins*
  • Neoplasm Recurrence, Local*
  • Polypeptide N-acetylgalactosaminyltransferase
  • Prognosis
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • N-Acetylgalactosaminyltransferases