Cancer cells exhibit profound alterations in their glycosylation machinery, resulting in distinctive glycan markers, which could be exploited for diagnosis purposes employing arrays. As the field of glycan-based precision medicine continues to evolve, these complex carbohydrate structures are revealing their critical role in cancer metastasis, immune evasion, and therapeutic resistance. [1] The aberrant glycosylation patterns observed in malignant cells represent a universal hallmark of cancer, providing both diagnostic opportunities and therapeutic targets that extend far beyond traditional protein-based approaches.[2] These modifications include several key structural changes:
Increased sialylation – enhances interactions with immune-inhibitory Siglec receptors.
Overexpression of complex branched N-glycans – creates glycan shields preventing immune recognition.
Hyper-fucosylation – facilitates immune evasion mechanisms.
Abnormal truncated O-glycans (such as Tn antigen) – recognized by immunosuppressive receptors.
These distinct structural variations in glycosylation present a valuable opportunity for the early identification and diagnosis of tumors. These glycan signatures often emerge during the initial stages of malignant transformation, making them highly informative biomarkers for cancer detection.[3] A variety of analytical techniques have been developed to detect these aberrant glycosylation patterns in cancer patients, including immunohistochemistry and mass spectrometry-based methods.[4] While these approaches offer high sensitivity and specificity, they can be time-consuming, technically demanding, and resource-intensive.
In contrast, the use of lectin and glycan arrays provides a rapid, cost-effective, and straightforward platform for simultaneously analyzing multiple glycosylation and binding patterns in biological samples. These array-based technologies enable high-throughput profiling of glycan alterations across a wide range of samples with minimal preparation, supporting efficient biomarker discovery and clinical application n cancer diagnostics.
Lectin Arrays
Lectin arrays consist of panels of multiple lectins immobilized on solid surfaces, typically glass slides or microfluidic chips, that can simultaneously analyze numerous lectin-glycan interactions in a single experiment.[5] This technology exploits the high specificity of lectins for carbohydrate recognition, allowing a comprehensive glycan profiling without requiring the release of glycans from glycoproteins. These arrays typically employ 14-96 different lectins with distinct binding specificities, enabling the detection of diverse glycan epitopes including N-linked and O-linked glycans, as well as glycolipids.
The methodology involves fluorescently labeling biological samples (serum, tissue extracts, or cell lysates) and incubating them with the lectin array. The resulting lectin-glycan interactions are quantified through fluorescence detection, generating comprehensive glycan profiles that can be used for comparative analysis between diseased and healthy states.
The clinical utility of lectin arrays extends beyond simple biomarker identification. These platforms offer several key advantages for cancer diagnosis: rapid analysis (results can be obtained within hours), high sensitivity (detecting low-abundance glycoproteins that conventional methods might miss), and comprehensive profiling (simultaneous analysis of multiple glycan epitopes). The technology is particularly valuable for identifying cancer-associated glycan biomarkers in complex biological fluids, where aberrant glycosylation patterns can serve as early indicators of malignant transformation.
Glycan Arrays
Glycan arrays have become essential in cancer diagnostics research due to their ability to comprehensively profile glycan–protein interactions and identify cancer-specific glycan signatures.[6] Contrary to lectin array, in this technology, glycans are immobilized on the surface of a chip and incubated with biological fluids. Glycan arrays are useful to screen serum anti-glycan antibodies for various cancers, providing a high-throughput, unbiased platform to identify novel disease-associated antibody subpopulations.
This approach is especially valuable when the relevant glycan targets are unknown, as it allows for simultaneous evaluation of a wide spectrum of glycan–antibody interactions using minimal sample volumes. Additionally, cancer-associated autoantibodies function as biological amplification systems that enable detection during the earliest phases of malignant transformation, preceding the appearance of detectable tumor antigens in circulation, making them exceptionally valuable for early cancer diagnosis.[7] The ongoing development of glycan arrays and related biosensors continues to expand their utility, offering promising avenues for early cancer detection, monitoring disease progression, and guiding personalized therapeutic strategies.
The field of glycan and lectin arrays has rapidly advanced in cancer diagnostics and translational research. Glycan arrays, which present a diverse repertoire of carbohydrate structures, and lectin arrays, which utilize the binding specificity of lectins to profile glycosylation, have collectively enabled high-throughput, sensitive, and detailed mapping of glycan signatures associated with malignancy. The nexttable summarizes some representative applications of lectin and glycan arrays in cancer diagnostics.
These technologies have proven particularly powerful in analyzing serum glycoproteins and tissue samples, revealing distinct glycan patterns that differentiate cancer from benign conditions and even distinguish among cancer subtypes. Additionally, to the application on cancer diagnosis, glycan and lectin arrays are being explored for used for autoimmunity and infectious diseases.
References
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- 2. Pinho, S. S., Macauley, M. S. & Läubli, H. Tumor glyco-immunology, glyco-immune checkpoints and immunotherapy. J. Immunother. Cancer 13, (2025).
- 3. Grzesik, K., Janik, M. & Hoja-Łukowicz, D. The hidden potential of glycomarkers: Glycosylation studies in the service of cancer diagnosis and treatment. Biochim. Biophys. Acta BBA – Rev. Cancer 1878, 188889 (2023).
- 4. Guo, Y., Jia, W., Yang, J. & Zhan, X. Cancer glycomics offers potential biomarkers and therapeutic targets in the framework of 3P medicine. Front. Endocrinol. 13, (2022).
- 5. Dang, K., Zhang, W., Jiang, S., Lin, X. & Qian, A. Application of Lectin Microarrays for Biomarker Discovery. ChemistryOpen 9, 285–300 (2020).
- 6. Marglous, S., Brown, C. E., Padler-Karavani, V., Cummings, R. D. & Gildersleeve, J. C. Serum antibody screening using glycan arrays. Chem. Soc. Rev. 53, 2603–2642 (2024).
- 7. Corzana, F. et al. Detection of Tumor-Associated Autoantibodies in the Sera of Pancreatic Cancer Patients Using Engineered MUC1 Glycopeptide Nanoparticle Probes. Angew. Chem. Int. Ed. 63, e202407131 (2024).
- 8. Liang, Y. et al. Stage-associated differences in the serum N- and O-glycan profiles of patients with non-small cell lung cancer. Clin. Proteomics 16, 20 (2019).
- 9. Qiu, Y. et al. Plasma Glycoprotein Profiling for Colorectal Cancer Biomarker Identification by Lectin Glycoarray and Lectin Blot. J. Proteome Res. 7, 1693–1703 (2008).
- 10. Qin, Y. et al. Alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV. Glycoconj. J. 33, 125–136 (2016).
- 11. Huflejt, M. E. et al. Detection of neoplasia-specific clusters of anti-glycan antibodies in sera of breast cancer patients using a novel glycan array. Cancer Res. 65, 1313 (2005).
- 12. Otto, J. J. et al. Gut immunoglobulin alpha anti-glycan binding profiles as a research tool for local disease detection. Glycoconj. J. 35, 333–342 (2018).
- 13. Wu, C.-S. et al. Cancer-Associated Carbohydrate Antigens as Potential Biomarkers for Hepatocellular Carcinoma. PLOS ONE 7, e39466 (2012).
- 14. Jacob, F. et al. Serum antiglycan antibody detection of nonmucinous ovarian
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