Upregulation of Glycans Containing 3′ Fucose in a Subset of Pancreatic Cancers Uncovered Using Fusion-Tagged LectinsClick to copy article linkArticle link copied!
- Sudhir Singh
- Kuntal Pal
- Jessica Yadav
- Huiyuan Tang
- Katie Partyka
- Doron Kletter
- Peter Hsueh
- Elliot Ensink
- Birendra KC
- Galen Hostetter
- H. Eric Xu
- Marshall Bern
- David F. Smith
- Anand S. Mehta
- Randall Brand
- Karsten Melcher
- Brian B. Haab
Abstract

The fucose post-translational modification is frequently increased in pancreatic cancer, thus forming the basis for promising biomarkers, but a subset of pancreatic cancer patients does not elevate the known fucose-containing biomarkers. We hypothesized that such patients elevate glycan motifs with fucose in linkages and contexts different from the known fucose-containing biomarkers. We used a database of glycan array data to identify the lectins CCL2 to detect glycan motifs with fucose in a 3′ linkage; CGL2 for motifs with fucose in a 2′ linkage; and RSL for fucose in all linkages. We used several practical methods to test the lectins and determine the optimal mode of detection, and we then tested whether the lectins detected glycans in pancreatic cancer patients who did not elevate the sialyl-Lewis A glycan, which is upregulated in ∼75% of pancreatic adenocarcinomas. Patients who did not upregulate sialyl-Lewis A, which contains fucose in a 4′ linkage, tended to upregulate fucose in a 3′ linkage, as detected by CCL2, but they did not upregulate total fucose or fucose in a 2′ linkage. CCL2 binding was high in cancerous epithelia from pancreatic tumors, including areas negative for sialyl-Lewis A and a related motif containing 3′ fucose, sialyl-Lewis X. Thus, glycans containing 3′ fucose may complement sialyl-Lewis A to contribute to improved detection of pancreatic cancer. Furthermore, the use of panels of recombinant lectins may uncover details about glycosylation that could be important for characterizing and detecting cancer.
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- Mithony Keng, Kenneth M. Merz, Jr.. In Silico Characterization of Glycan Ions from IM-MS Collision Cross Section. Journal of the American Society for Mass Spectrometry 2025, Article ASAP.
- Hock-Seng Nguan, Jien-Lian Chen, Chi-Kung Ni. Collision-Induced Dissociation of Fucose and Identification of Anomericity. The Journal of Physical Chemistry A 2024, 128
(19)
, 3812-3820. https://doi.org/10.1021/acs.jpca.4c00640
- Erika Lattová, Jana Skřičková, Zbyněk Zdráhal. Applicability of Phenylhydrazine Labeling for Structural Studies of Fucosylated N-Glycans. Analytical Chemistry 2019, 91
(13)
, 7985-7990. https://doi.org/10.1021/acs.analchem.9b01321
- Christa M. Snyder, William R. Alley, Jr., Margit I. Campos, Martin Svoboda, John A. Goetz, Jaqueline A. Vasseur, Stephen C. Jacobson, and Milos V. Novotny . Complementary Glycomic Analyses of Sera Derived from Colorectal Cancer Patients by MALDI-TOF-MS and Microchip Electrophoresis. Analytical Chemistry 2016, 88
(19)
, 9597-9605. https://doi.org/10.1021/acs.analchem.6b02310
- Yuri van der Burgt, Manfred Wuhrer. The Role of Clinical Glyco(proteo)mics in Precision Medicine. Molecular & Cellular Proteomics 2023, 22
(6)
, 100565. https://doi.org/10.1016/j.mcpro.2023.100565
- Yuanwei Xu, Yuefan Wang, Naseruddin Höti, David J. Clark, Shao‐Yung Chen, Hui Zhang. The next “sweet” spot for pancreatic ductal adenocarcinoma: Glycoprotein for early detection. Mass Spectrometry Reviews 2023, 42
(2)
, 822-843. https://doi.org/10.1002/mas.21748
- Michael P. Marciel, Barnita Haldar, Jihye Hwang, Nikita Bhalerao, Susan L. Bellis. Role of tumor cell sialylation in pancreatic cancer progression. 2023, 123-155. https://doi.org/10.1016/bs.acr.2022.07.003
- Jan C. Lumibao, Jacob R. Tremblay, Jasper Hsu, Dannielle D. Engle. Altered glycosylation in pancreatic cancer and beyond. Journal of Experimental Medicine 2022, 219
(6)
https://doi.org/10.1084/jem.20211505
- I.J.M. Levink, D.C.F. Klatte, R.G. Hanna-Sawires, G.C.M. Vreeker, I.S. Ibrahim, Y.E.M. van der Burgt, K.A. Overbeek, B.D.M. Koopmann, D.L. Cahen, G.M. Fuhler, M. Wuhrer, B.A. Bonsing, R.A.E.M. Tollenaar, F.P. Vleggaar, H.F.A. Vasen, M.E. van Leerdam, M.J. Bruno, W.E. Mesker. Longitudinal changes of serum protein N-Glycan levels for earlier detection of pancreatic cancer in high-risk individuals. Pancreatology 2022, 38 https://doi.org/10.1016/j.pan.2022.03.021
- Katherine S. Yang, Debora Ciprani, Aileen O’Shea, Andrew S. Liss, Robert Yang, Sarah Fletcher-Mercaldo, Mari Mino-Kenudson, Carlos Fernández-del Castillo, Ralph Weissleder. Extracellular Vesicle Analysis Allows for Identification of Invasive IPMN. Gastroenterology 2021, 160
(4)
, 1345-1358.e11. https://doi.org/10.1053/j.gastro.2020.11.046
- Colin T. McDowell, Zachary Klamer, Johnathan Hall, Connor A. West, Luke Wisniewski, Thomas W. Powers, Peggi M. Angel, Anand S. Mehta, David N. Lewin, Brian B. Haab, Richard R. Drake. Imaging Mass Spectrometry and Lectin Analysis of N-Linked Glycans in Carbohydrate Antigen–Defined Pancreatic Cancer Tissues. Molecular & Cellular Proteomics 2021, 20 , 100012. https://doi.org/10.1074/mcp.RA120.002256
- Eiji Miyoshi, Koichi Morishita, Tatsuya Asuka, Tomoya Fukuoka, Shinji Takamatsu, Yoshihiro Kamada, Miyako Nakano. Glycan Biomarkers in Pancreatic Cancer. 2021, 471-482. https://doi.org/10.1016/B978-0-12-409547-2.14945-5
- Ben Staal, Ying Liu, Daniel Barnett, Peter Hsueh, Zonglin He, ChongFeng Gao, Katie Partyka, Mark W. Hurd, Aatur D. Singhi, Richard R. Drake, Ying Huang, Anirban Maitra, Randall E. Brand, Brian B. Haab. The sTRA Plasma Biomarker: Blinded Validation of Improved Accuracy Over CA19-9 in Pancreatic Cancer Diagnosis. Clinical Cancer Research 2019, 25
(9)
, 2745-2754. https://doi.org/10.1158/1078-0432.CCR-18-3310
- Matthew T. Briggs, Mark R. Condina, Manuela Klingler‐Hoffmann, Georgia Arentz, Arun V. Everest‐Dass, Gurjeet Kaur, Martin K. Oehler, Nicolle H. Packer, Peter Hoffmann. Translating
N‐
Glycan Analytical Applications into Clinical Strategies for Ovarian Cancer. PROTEOMICS – Clinical Applications 2019, 13
(3)
https://doi.org/10.1002/prca.201800099
- Montserrat Mancera-Arteu, Estela Giménez, Meritxell Balmaña, Sílvia Barrabés, Maite Albiol-Quer, Esther Fort, Rosa Peracaula, Victòria Sanz-Nebot. Multivariate data analysis for the detection of human alpha-acid glycoprotein aberrant glycosylation in pancreatic ductal adenocarcinoma. Journal of Proteomics 2019, 195 , 76-87. https://doi.org/10.1016/j.jprot.2019.01.006
- Jennifer Munkley. The glycosylation landscape of pancreatic cancer (Review). Oncology Letters 2019, https://doi.org/10.3892/ol.2019.9885
- Esther Llop, Pedro E Guerrero, Adrià Duran, Sílvia Barrabés, Anna Massaguer, María José Ferri, Maite Albiol-Quer, Rafael de Llorens, Rosa Peracaula. Glycoprotein biomarkers for the detection of pancreatic ductal adenocarcinoma. World Journal of Gastroenterology 2018, 24
(24)
, 2537-2554. https://doi.org/10.3748/wjg.v24.i24.2537
- H. Benachour, J. Leroy‐Dudal, R. Agniel, J. Wilson, M. Briand, F. Carreiras, O. Gallet. Vitronectin (Vn) glycosylation patterned by lectin affinity assays—A potent glycoproteomic tool to discriminate plasma Vn from cancer ascites Vn. Journal of Molecular Recognition 2018, 31
(5)
https://doi.org/10.1002/jmr.2690
- Montserrat Mancera-Arteu, Estela Giménez, José Barbosa, Rosa Peracaula, Victòria Sanz-Nebot. Zwitterionic-hydrophilic interaction capillary liquid chromatography coupled to tandem mass spectrometry for the characterization of human alpha-acid-glycoprotein N -glycan isomers. Analytica Chimica Acta 2017, 991 , 76-88. https://doi.org/10.1016/j.aca.2017.07.068
- Elizabeth Hull, McKale Montgomery, Kathryn Leyva. Epigenetic Regulation of the Biosynthesis & Enzymatic Modification of Heparan Sulfate Proteoglycans: Implications for Tumorigenesis and Cancer Biomarkers. International Journal of Molecular Sciences 2017, 18
(7)
, 1361. https://doi.org/10.3390/ijms18071361
- Yaogang Zhong, Yonghong Guo, Xiawei Liu, Jiaxu Zhang, Tianran Ma, Jian Shu, Jiajun Yang, Jing Zhang, Zhansheng Jia, Zheng Li. Serum Glycopatterns as Novel Potential Biomarkers for Diagnosis of Acute-on-Chronic Hepatitis B Liver Failure. Scientific Reports 2017, 7
(1)
https://doi.org/10.1038/srep45957
- Silvia Bleuler-Martinez, Katrin Stutz, Ramon Sieber, Mayeul Collot, Jean-Maurice Mallet, Michael Hengartner, Mario Schubert, Annabelle Varrot, Markus Künzler. Dimerization of the fungal defense lectin CCL2 is essential for its toxicity against nematodes. Glycobiology 2016, 1853 https://doi.org/10.1093/glycob/cww113
- Montserrat Mancera-Arteu, Estela Giménez, José Barbosa, Victòria Sanz-Nebot. Identification and characterization of isomeric N-glycans of human alfa-acid-glycoprotein by stable isotope labelling and ZIC-HILIC-MS in combination with exoglycosidase digestion. Analytica Chimica Acta 2016, 940 , 92-103. https://doi.org/10.1016/j.aca.2016.07.043
- Mengjun Wang, Mary Ann Comunale, Harmin Herrera, Lucy Betesh, Yuko Kono, Anand Mehta. Identification of IgM as a contaminant in lectin-FLISA assays for HCC detection. Biochemical and Biophysical Research Communications 2016, 476
(3)
, 140-145. https://doi.org/10.1016/j.bbrc.2016.05.027
- Huiyuan Tang, Katie Partyka, Peter Hsueh, Jessica Y. Sinha, Doron Kletter, Herbert Zeh, Ying Huang, Randall E. Brand, Brian B. Haab. Glycans Related to the CA19-9 Antigen Are Increased in Distinct Subsets of Pancreatic Cancers and Improve Diagnostic Accuracy Over CA19-9. Cellular and Molecular Gastroenterology and Hepatology 2016, 2
(2)
, 210-221.e15. https://doi.org/10.1016/j.jcmgh.2015.12.003
- M. Luísa S. Silva. Cancer serum biomarkers based on aberrant post-translational modifications of glycoproteins: Clinical value and discovery strategies. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2015, 1856
(2)
, 165-177. https://doi.org/10.1016/j.bbcan.2015.07.002
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