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Peer-reviewedCC BY-NC-ND 4.0Proceedings of the National Academy of Sciences of the United States of America

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

4 affiliations
  1. 1State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry, Nanjing University, Nanjing, Jiangsu 210023, China
  2. 2Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China
  3. 3Department of Nuclear Medicine, Nanjing Drum Tower Hospital, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China
  4. 4Comprehensive Cancer Center, Nanjing Drum Tower Hospital, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China

Abstract

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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BibTeX
@article{huang2026glycan,
  title = {{A glycan superbinder reveals polysialylated-CD56 as a precision biomarker for pancreatic cancer}},
  author = {Lingrui Huang and Song Gao and Qi Li and Fang Jin and Anqi Zhang and Xiawen Lin and Yanrong Wen and Wenyan Guan and Jie Shen and Jian He and Zhen Liu},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year = {2026},
  month = oct,
  doi = {10.1073/pnas.2611747123},
  url = {https://doi.org/10.1073/pnas.2611747123},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - A glycan superbinder reveals polysialylated-CD56 as a precision biomarker for pancreatic cancer
AU  - Lingrui Huang
AU  - Song Gao
AU  - Qi Li
AU  - Fang Jin
AU  - Anqi Zhang
AU  - Xiawen Lin
AU  - Yanrong Wen
AU  - Wenyan Guan
AU  - Jie Shen
AU  - Jian He
AU  - Zhen Liu
PY  - 2026
DA  - 2026/10/28
JO  - Proceedings of the National Academy of Sciences of the United States of America
DO  - 10.1073/pnas.2611747123
UR  - https://doi.org/10.1073/pnas.2611747123
AB  - 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.
SN  - 0027-8424
SN  - 1091-6490
ER  -