Prognostic utility of glycosyltransferase expression in breast cancer.
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.


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.


CONCLUSIONS
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.
Patani
Neill
N
The London Breast Institute, The Princess Grace Hospital, London, UK.
Jiang
Wen
W
Mokbel
Kefah
K
D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017350:N-Acetylgalactosaminyltransferases / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011237:Predictive Value of Tests; D012799:Sialyltransferases / Q000096:biosynthesis*; D015996:Survival Rate; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D009363:Neoplasm Proteins; D017350:N-Acetylgalactosaminyltransferases; C121529:UDP-N-acetylgalactosamine polypeptide N-acetylgalactosaminyltransferase 6; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase