Multiplexed biosensing diagnostic platforms detecting autoantibodies to tumor-associated antigens from exosomes released by CRC cells and tissue samples showed high diagnostic ability for colorectal cancer

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Montero Calle, Ana and Aranguren Abeigon, Itziar and Garranzo Asensio, María and Povés Francés, Carmen and Fernández Aceñero, María Jesús and Martínez Useros, Javier and Sanz, Rodrigo and Dziaková, Jana and Rodríguez Cobos, Javier and Solís Fernández, Guillermo and Povedano, Eloy and Gamella Carballo, Maria and Torrente Rodríguez, Rebeca Magnolia and Alonso Navarro, Miren and Ríos, Vivian de los and Casal, J. Ignacio and Domínguez Muñóz, Gemma and Guzmán Aránguez, Ana Isabel and Peláez García, Alberto, Alberto and Pingarrón Carrazón, José Manuel and Campuzano Ruiz, Susana and Barderas Manchado, Rodrigo (2021) Multiplexed biosensing diagnostic platforms detecting autoantibodies to tumor-associated antigens from exosomes released by CRC cells and tissue samples showed high diagnostic ability for colorectal cancer. Engineering . ISSN 2095-8099; 2096-0026 (e) (In Press)

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Official URL: https://doi.org/10.1016/j.eng.2021.04.026




Abstract

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. The 5-year survival rate of CRC patients depends on the stage at diagnosis, being higher than 80% when CRC is diagnosed in the early stages but lower than 10% when CRC is diagnosed in advanced stages. Autoantibodies against specific CRC autoantigens (tumor-associated antigens (TAAs)) in the sera of patients have been widely demonstrated to aid in early diagnosis. Thus, we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy. To that end, we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis. A total of 103 proteins were identified as potential autoantigens specific to CRC. After bioinformatics and meta-analysis, we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot (WB) and immunohistochemistry (IHC). We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients, along with an association of nine of these proteins with CRC prognosis. After validation, all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals, either by luminescence Halotag-based beads, or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC detection. Taken together, our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases; they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care (POC) device for CRC detection with high diagnostic ability.


Item Type:Article
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Received: 30 September 2020 / Revised: 5 February 2021 / Accepted: 27 April 2021 / Available online: 14 August 2021.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Uncontrolled Keywords:Autoantibodies; Diagnosis; Colorectal cancer; Exosomes; Tumor microenviroment; Humoral immune response; Point of care; Biosensors
Subjects:Medical sciences > Medicine > Gastroenterology and Hepatology
Medical sciences > Medicine > Oncology
ID Code:67615
Deposited On:09 Sep 2021 15:10
Last Modified:10 Sep 2021 07:43

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