Microarray Glycoprofiling of CA125 improves differential diagnosis of ovarian cancer.
The CA125 biomarker assay plays an important role in the diagnosis and management of primary invasive epithelial ovarian/tubal cancer (iEOC). However, a fundamental problem with CA125 is that it is not cancer-specific and may be elevated in benign gynecological conditions such as benign ovarian neoplasms and endometriosis. Aberrant O-glycosylation is an inherent and specific property of cancer cells and could potentially aid in differentiating cancer from these benign conditions, thereby improving specificity of the assay. We report on the development of a novel microarray-based platform for profiling specific aberrant glycoforms, such as Neu5Acα2,6GalNAc (STn) and GalNAc (Tn), present on CA125 (MUC16) and CA15-3 (MUC1). In a blinded cohort study of patients with an elevated CA125 levels (30-500 kU/L) and a pelvic mass from the UK Ovarian Cancer Population Study (UKOPS), we measured STn-CA125, ST-CA125 and STn-CA15-3. The combined glycoform profile was able to distinguish benign ovarian neoplasms from invasive epithelial ovarian/tubule cancer (iEOCs) with a specificity of 61.1% at 90% sensitivity. The findings suggest that microarray glycoprofiling could improve differential diagnosis and significantly reduce the number of patients elected for further testing. The approach warrants further investigation in other cancers.
Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine and School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Kowa
K
Chen
Aleksandra
A
Gentry-Maharaj
Matthew
M
Burnell
Catharina
C
Steentoft
Lara
L
Marcos-Silva
Ulla
U
Mandel
Ian
I
Jacobs
Anne
A
Dawnay
Usha
U
Menon
Ola
O
Blixt
D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D018394:CA-125 Antigen / Q000097:blood / Q000235:genetics*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D018396:Mucin-1 / Q000097:blood / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000473:pathology
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C060192:MUC1 protein, human; D018396:Mucin-1