Multiplex Determination\nof Glycan Profiles on Urinary\nProstate-Specific Antigen by Quartz-Crystal Microbalance Combined\nwith Surface-Enhanced Raman Scattering

Prostate cancer remains a major health concern, with\nprostate-specific\nantigen (PSA) being a key biomarker for its detection and monitoring.\nHowever, PSA levels often fall into a “gray zone”, where\nPSA levels are not clearly indicative of cancer, thus complicating\nearly diagnosis and treatment decisions. Glycosylation profiles, which\noften differ between healthy and diseased cells, have emerged as potential\nbiomarkers to enhance the specificity and sensitivity of cancer diagnosis\nin these ambiguous cases. We propose the integration of two complementary\ntechniques, namely quartz-crystal microbalance with dissipation (QCM-D)\nand surface-enhanced Raman scattering (SERS) to study PSA glycan profiles.\nQCM-D offers real-time operation, PSA mass quantification, and label-free\ndetection with high sensitivity, as well as enhanced specificity and\nreduced cross-reactivity when using nucleic acid aptamers as capture\nligands. Complementary SERS sensing enables the determination of the\nglycosylation pattern on PSA, at low concentrations and without the\ndrawbacks of photobleaching, thereby facilitating multiplexed glycosylation\npattern analysis. This integrated setup could retrieve a data set\ncomprising analyte concentrations and associated glycan profiles in\nrelevant biological samples, which may eventually improve early disease\ndetection and monitoring. Prostate-specific antigen (PSA), a glycoprotein\nsecreted by prostate epithelial cells, serves as our proof-of-concept\nanalyte. Our platform allows multiplex targeting of PSA multiplex\nglycosylation profiles of PSA at “gray zone” concentrations\nfor prostate cancer diagnosis. We additionally show the use of SERS\nfor glycan analysis in PSA secreted from prostate cancer cell lines\nafter androgen-based treatment. Differences in PSA glycan profiles\nfrom resistant cell lines after androgen-based treatment may eventually\nimprove cancer treatment.