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 α6-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.