Prognostic utility of glycosyltransferase expression in breast cancer.

Abstract

BACKGROUND:

The post-translational modification of proteins, including glycosylation, is known to differ between normal and tumour cells. In this study, the expression profile of two glycosyltranferases, UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6) and alpha6-sialyl-transferase-I (ST6GalNAc-I) was assessed, in a cohort of women with breast cancer.

PATIENTS AND METHODS:

Breast cancer tissues (n=127) and normal background tissues (n=33) were collected immediately after excision during surgery. Following RNA extraction, reverse transcription was carried out and transcript levels were determined using real-time quantitative PCR and normalized against glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression. Transcript levels within the breast cancer specimens were compared to the normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period.

RESULTS:

Significantly higher levels of ppGalNAc-T6 were found in the breast cancer specimens compared to the background tissue (p=0.015). There was a non-significant trend for levels to increase with the Nottingham Prognostic Index (NPI) and TNM stage and those who died from breast cancer. ST6GalNAc-I expression was associated with better prognosis, reaching significance when comparing patients who remained disease free to those with distant recurrence (p=0.0096). The relationship approached significance when comparing NPI 2 to NPI 3 (p=0.058) and disease free patients to non-disease free patients (p=0.052) or those who died of breast cancer (p=0.060). For both enzymes a significant association with ductal type was found.

CONCLUSION:

Expression of ppGalNAc-T6 is significantly higher in breast cancer compared to 'normal'/benign breast tissue samples. ST6GalNAc-I expression in breast cancer is associated with better prognosis.

• Authors: Neill Patani, Wen Jiang, Kefah Mokbel
• Journal: Cancer genomics & proteomics (Cancer Genomics Proteomics) 2008 Nov-Dec Vol. 5 Issue 6 Pg. 333-40 ISSN: 1109-6535 [Print] Greece
• PMID: 19287074 (Publication Type: Journal Article)

Chemical References

• Neoplasm Proteins
• N-Acetylgalactosaminyltransferases
• UDP-N-acetylgalactosamine polypeptide N-acetylgalactosaminyltransferase 6
• Sialyltransferases
• beta-D-Galactoside alpha 2-6-Sialyltransferase

Topics

• Breast Neoplasms (enzymology, mortality)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• N-Acetylgalactosaminyltransferases (biosynthesis)
• Neoplasm Proteins (biosynthesis)
• Predictive Value of Tests
• Sialyltransferases (biosynthesis)
• Survival Rate
• beta-D-Galactoside alpha 2-6-Sialyltransferase