The
CA 19-9 antigen is currently the best individual marker for the detection of
pancreatic cancer. In order to optimize the CA 19-9 assay and to develop approaches to further improve
cancer detection, it is important to understand the specificity differences between CA 19-9
antibodies and the consequential affect on
biomarker performance. Antibody arrays enabled multiplexed comparisons between five different CA 19-9
antibodies used in the analysis of plasma samples from
pancreatic cancer patients and controls. Major differences were observed between
antibodies in their detection of particular patient samples.
Glycan array analysis revealed that certain
antibodies were highly specific for the canonical CA 19-9
epitope,
sialyl-Lewis A, while others bound
sialyl-Lewis A in addition to a related structure called sialyl-Lewis C and modification with Nue5Gc. In a much larger patient cohort, we confirmed the binding of sialyl-Lewis C
glycan by one of the
antibodies and showed that the broader specificity led to the detection of an increased number of
cancer patients without increasing detection of
pancreatitis patient samples. This work demonstrates that variation between antibody specificity for
cancer-associated
glycans can have significant implications for
biomarker performance and highlights the value of characterizing and detecting the range of
glycan structures that are elevated in
cancer.