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

| Source: Proceedings of the National Academy of Sciences of the United States of America

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 s

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.

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