Aptamer-based Glycan PSA Score for Discrimination of Prostate Cancer from other Prostate Diseases

Ana Diaz-Fernandez, Rebeca Miranda-Castro, Noemi de los Santos Alvarez, Maria Jesus Lobo Castanon, Pedro Estrela

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Abstract

Prostate specific antigen (PSA) is the common biomarker for prostate cancer (PCa). However, its lack of specificity to differentiate PCa from benign prostate disorders stimulates the search for alternative cancer biomarkers to improve the clinical management of the patients. Different studies have described changes in the core-fucosylation level of PSA between PCa patients and healthy controls. To exploit these findings, we have adapted an impedimetric aptamer-based sensor to the dual recognition of PSA. Two different aptamers, PSAG-1 and anti-PSA, are immobilized onto two adjacent nanostructured gold electrodes. The direct binding from diluted serum samples of specific glycosylated-PSA to the first sensor and total PSA to the second one leads to changes in the charge transfer resistance, which correlate to the amount of glycosylated and total PSA in the sample. The sensors are able to measure PSA in serum with a dynamic range between 0.26 and 62.5 ng/mL (PSAG-1) and from 0.64 to 62.5 ng/mL (anti-PSA), with a reproducibility of 5.4 %. The final output of the proposed platform is the ratio between PSAG-1 reactive PSA and total PSA, defined as the glycan score. The glycan score was tested in serum samples from patients with different pathologies, showing excellent correlation between the measured score and the known diagnosis of the patients. Hence this dual aptamer-based impedimetric biosensor could be used as a minimally invasive method for the diagnosis of prostate cancer.
Original languageEnglish
Article number112872
JournalBiosensors and Bioelectronics
Volume175
Early online date29 Nov 2020
DOIs
Publication statusPublished - 1 Mar 2021

Funding

Although the immobilization of the aptamers, with the corresponding conformational constrains, leads to a reduction in their affinity towards the protein, the magnitude of this effect is different in both cases. While the affinity of anti-PSA diminished by two-fold, that of PSAG-1 decreased by more than 100 times. There are two potentially significant differences. First, both aptamers recognize different epitopes on the protein, with different accessibility. Second, the hPSA standard used for titration may contain different glycosylation forms, and it has been previously found that about 77% of the standard PSA isolated from seminal fluid carries core-fucosylated N-glycans (Llop et al., 2016). Nevertheless, the obtained affinities support PSA measurements across the clinical range.We thank Dr. E. Fern?ndez-Rodr?guez and Dr. S. Garc?a-Alonso (Hospital Universitario de Cabue?es-Asturias) for providing the serum samples. The work was funded by the Spanish Ministerio de Ciencia y Universidades (RTI-2018-095756-B-I00), and Principado de Asturias Government (IDI2018-000217), co-financed by FEDER funds. A.D.F. was supported by Asociaci?n Espa?ola contra el C?ncer (AECC) with a Ph.D. fellowship and by Banco Santander and University of Oviedo with a grant in the framework of the economic mobility of excellence grants for teachers and researchers.

Keywords

  • Aptasensor
  • Glycosylation pattern
  • Impedimetric sensor
  • Prostate cancer
  • PSA

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