Cancer is a group of diseases characterized by a wide diversity in location, cellular features and aggressiveness. Nonetheless, a common aspect seen in different types of cancer, namely in carcinomas, is the alteration in post-translational modifications of proteins, particularly in protein glycosylation . Due to increased or decreased expression of particular enzymes participating in glycosylation of proteins, different glycan structures are formed, which are typical of tumoral cells. When the respective glycoproteins are secreted into the blood stream, these aberrant structures can be used as valuable cancer biomarkers, since they are not synthesized by normal cells.
Glycan structures are efficiently and selectively detected by lectins, which are proteins of natural origin with high affinity for a particular or a very small group of glycan epitopes. Lectins are used for glycan detection as antibodies are used for protein recognition. Therefore, they have been employed in diverse analytical techniques when the aim is to selectively detect or capture specific glycans from a complex sample.
Lectin biosensors are attractive devices for the detection of cancer-associated glycobiomarkers in serum since they combine the advantageous aspects of biosensors (portability, easy use in point-of-care analysis, low sample requirement) with the high selectivity of lectin biorecognition. This work presents three lectin-based impedimetric biosensors for the selective detection of specific aberrant cancer-associated O-glycans, namely STn, Tn and T antigens, which are well-established pan-carcinoma biomarkers. For these three biosensors, Sambucus nigra agglutinin, Vicia villosa agglutinin and Arachis hypogeae agglutinin were used as biorecognition elements, with specificity for STn, Tn and T antigens, respectively. The binding event between each lectin and the corresponding aberrant O-glycan was monitored by electrochemical impedance spectroscopy, measuring the increase in the biosensor’s impedance after incubating the samples. The increase in impedance was related to the lectin-glycan complex formation.
All biosensors were constructed following the same general procedure, demonstrating its high versatility. A thorough characterization and validation of the biosensors’ performance was carried out, evaluation their selectivity, sensitivity and ability to discriminate between samples from healthy donors and from cancer patients with different carcinomas. Using the three lectin biosensors in the analysis of the same sample could also help to characterize the glycosylation profiles of glycoproteins in the diverse types of carcinomas.
 Pinho S.S., Reis C.A. Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer 15 (2015) 540-555.