Levels of specific serum N-glycans identify breast cancer patients with higher circulating tumor cell counts.
BACKGROUND
Metastatic breast cancer (MBC) is currently an incurable condition that is primarily treated with palliative measures. Isolation of circulating tumor cells (CTCs) from the peripheral blood of these patients provides a predictive prognostic indicator, independent of the type of therapy, site of occurrence and biological characteristics of the primary disease. It has been well established that glycosylation processing pathways are disturbed in cancer, leading to alterations in the glycan content of glycoproteins.


METHODS
The bi-, tri- and tetraantennary glycans containing sialyl Lewis x (sLe(x)) epitopes (A2F1G1, A3F1G1, A4F1G1 and A4F2G2) were quantified using normal phase high-performance liquid chromatography in combination with exoglycosidase array digestions in the glycan pools released from sera of 27 patients with advanced breast cancer (16 with CTCs <5/7.5 ml and 11 with CTCs ≥5/7.5 ml) and 13 healthy women.


RESULTS
The levels of all these glycans were significantly higher in patients with CTCs ≥5/7.5 ml compared with patients with CTCs <5/7.5 ml.


CONCLUSIONS
As high levels of glycans containing sLe(x) epitopes were associated with CTCs, their measurement may provide a new noninvasive approach for determining prognosis in women with MBC.
NIBRT Dublin-Oxford Glycobiology Laboratory, The National Institute for Bioprocessing Research and Training, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
R
R
Saldova
Departments of Hematopathology.
J M
JM
Reuben
NIBRT Dublin-Oxford Glycobiology Laboratory, The National Institute for Bioprocessing Research and Training, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
U M
UM
Abd Hamid
NIBRT Dublin-Oxford Glycobiology Laboratory, The National Institute for Bioprocessing Research and Training, Conway Institute, University College Dublin, Belfield, Dublin, Ireland. Electronic address: pauline.rudd@nibrt.ie.
P M
PM
Rudd
Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
M
M
Cristofanilli
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology; D016022:Case-Control Studies; D002452:Cell Count; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009844:Oligosaccharides / Q000097:blood*; D011379:Prognosis; D000080506:Sialyl Lewis X Antigen
D014408:Biomarkers, Tumor; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen