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

Autor: Miren Alonso-Navarro, Maria Gamella, Gemma Domínguez, Rodrigo Sanz, Javier Rodríguez-Cobos, María Jesús Fernández-Aceñero, J. Ignacio Casal, Carmen Poves, Rebeca M. Torrente-Rodríguez, María Garranzo-Asensio, Itziar Aranguren-Abeigon, José M. Pingarrón, Alberto Peláez-García, Vivian de los Ríos, Guillermo Solís-Fernández, Jana Dziaková, Ana Montero-Calle, Ana Guzman-Aranguez, Eloy Povedano, Rodrigo Barderas, Susana Campuzano, Javier Martínez-Useros
Přispěvatelé: Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Comunidad de Madrid, Ministerio de Educación, Cultura y Deporte (España), Research Foundation - Flanders, Ministerio de Economía y Competitividad (España), Garranzo Asensio, María, Povés, Carmen, Fernandez-Aceñero, M. Jesús, Martínez-Useros, Javier, Dziaková, Jana, Solís-Fernández, Guillermo, Gamella, María, Alonso-Navarro, Miren, Ríos, Vivian de los, Casal, J. Ignacio, Domínguez-Muñoz, Gemma, Guzmán-Aránguez, Ana I., Peláez-García, Alberto, Pingarrón, José Manuel, Campuzano, Susana, Barderas, Rodrigo, Garranzo Asensio, María [0000-0003-0850-4986], Povés, Carmen [0000-0001-9800-3039], Fernandez-Aceñero, M. Jesús [0000-0002-2439-3553], Martínez-Useros, Javier [0000-0001-9007-828X], Dziaková, Jana [0000-0001-5317-5275], Solís-Fernández, Guillermo [0000-0002-4785-0040], Gamella, María [0000-0002-5408-118X], Alonso-Navarro, Miren [0000-0001-9406-4598], Ríos, Vivian de los [0000-0001-5582-6879], Casal, J. Ignacio [0000-0003-1085-2840], Domínguez-Muñoz, Gemma [0000-0002-1246-0528], Guzmán-Aránguez, Ana I. [0000-0001-6722-2044], Peláez-García, Alberto [0000-0002-5401-3216], Pingarrón, José Manuel [0000-0003-2271-1383], Campuzano, Susana [0000-0002-9928-6613], Barderas, Rodrigo [0000-0003-3539-7469], Autonomous University of Madrid (España), Comunidad de Madrid (España)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Engineering, Vol 7, Iss 10, Pp 1393-1412 (2021)
Digital.CSIC. Repositorio Institucional del CSIC
instname
Digital.CSIC: Repositorio Institucional del CSIC
Consejo Superior de Investigaciones Científicas (CSIC)
Repisalud
Instituto de Salud Carlos III (ISCIII)
E-Prints Complutense. Archivo Institucional de la UCM
ISSN: 2095-8099
Popis: 20 p.-9 fig.-2 tab.
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.
This work was supported by the financial support of the PI17CIII/00045 and PI20CIII/00019 grants from the AES-ISCIII program to R.B. The financial support of the PID2019-103899RB-I00 (Ministerio de Ciencia e Innovación) Research Project and the TRANSNANOAVANSENS-CM Program from the Comunidad de Madrid (S2018/NMT-4349) to S.C. are gratefully acknowledged. G.D. acknowledges the financial support of PI15/00246 grant of the FIS and Cátedra UAM-Roche en Medicina de Innovación. The FPU predoctoral contract to A.M-C. is supported by the Spanish Ministerio de Educación, Cultura y Deporte. G.S-F. is recipient of a predoctoral contract (1193818N) supported by The Flanders Research Foundation (FWO). M.A-N. was supported by a contract of the Programa Operativo de Empleo Juvenily la Iniciativa de Empleo Juvenil (YEI) with the participation of the Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid y del Fondo Social Europeo. The predoctoral contract from the Spanish Ministerio de Economía y Competitividad (BES-2016-076606, E.P.) and Talento-Contract from Comunidad de Madrid (2019-T2/IND-15965, R.M.T-R.) are also gratefully acknowledged.
Databáze: OpenAIRE
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