Microarray Glycoprofiling of CA125 Improves Differential Diagnosis of Ovarian Cancer

Abstract

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.

CA-125 of fetal origin can act as a ligand for dendritic cell-specific ICAM-3-grabbing non-integrin

“…Thus, the main differences between pregnancy-and cancerassociated CA-125 were attributed to N-glycan-associated structures reactive with ConA and PHA-E (phytohemagglutinin-E), as well as glyco-structures reactive with SBA (Glycine max agglutinin), SNA (Sambucus nigra agglutinin) and WFA (Wisteria floribunda agglutinin), as evaluated by their lectin-binding patterns [24,25,29]. Generally, the existence of various CA-125 forms was also supported by recent data obtained using microarray glycoprofiling, mass spectrometry, and HPLC [30,31]. Thus, under the experimental conditions applied, CA-125 heterogeneity was also observed concerning glyco-structures that are supposed to react with DC-SIGN.…”

A Nanoparticle-Lectin Immunoassay Improves Discrimination of Serum CA125 from Malignant and Benign Sources

“…The obtained binding patterns illustrate the existence of subtle differences in glycosylation between the 3 CA125 preparations studied. Using an antibody capture based microarray for the analysis of serum CA125, Chen et al (16 ) showed that GalNAc ␣ (Tn) specific MAbs and lectins such as VVL can be used to measure GalNAc ␣ (Tn) structures in CA125 that are present in EOC, while in our study VVL bound poorly only to Pla-CA125. The discrepancy between the results is not known.…”

“…Techniques including mass spectrometry, nuclear magnetic resonance, and chromatographic glycoprofiling have enabled analyses of the glycan structures present in cancer cells, sera and tissues (7, 9 -11 ). Such approaches have been used to identify potential glycan markers for prostate (12 ), breast (13 ), liver (14 ), and ovarian cancers (9,(15)(16).…”

Immunohistological Insight into the Correlation between Neuropilin-1 and Epithelial-Mesenchymal Transition Markers in Epithelial Ovarian Cancer

“…Mucins are proteins found to be highly expressed in EOCs and their glycosylated extracellular domain, which may overhang up to 200-2000 nm above the cell surface, has been associated with the dissemination and invasion of ovarian cancer cells. Recently, it has been shown that glycoprofiling of mucin 16 (MUC16), also known as CA125, improves the differential diagnosis of ovarian cancer (Chauhan et al 2009;Chen et al 2013). However, although CA125 was previously identified as an ovarian cancer diagnostic biomarker, it may not have the sensitivity or specificity to function alone in EOC screening (Cannistra 2004).…”