A glycan superbinder reveals polysialylated-CD56 as a precision biomarker for pancreatic cancer

Pancreatic cancer remains one of the most lethal malignancies, largely due to the lack of reliable biomarkers for early detection. Aberrant glycosylation presents a promising source of diagnostic signatures, yet polysialic acid (polySia), a distinctive glycan, has remained underexplored, primarily owing to limitations in detection methods and recognition tools. Here, we report the development of a polySia "superbinder," a nanoscale molecularly imprinted polymer (nanoMIP) that exhibits superior specificity and affinity for polySia over monoclonal antibodies, enabling precise recognition and quantification of this glycan. Leveraging this superbinder, we uncover a previously unrecognized association between polySia and pancreatic cancer and establish polysialylated CD56 (polySia-CD56) as a specific and robust biomarker. PolySia-CD56 outperforms multiple previously reported pancreatic cancer biomarkers, including the clinical standard carbohydrate antigen 19-9 (CA19-9). Notably, its expression pattern is complementary to that of CA19-9, and the combined use of both biomarkers significantly enhances diagnostic accuracy to 94.1%, effectively addressing the limitation of CA19-9 in detecting CA19-9-negative patients. Together, this study not only identifies polySia-CD56 as a precise biomarker for pancreatic cancer but also highlights the potential of antiglycan nanoMIPs as transformative reagents for decoding glycosylated targets and advancing clinical translation.