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
Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. The five-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. Autoantib...
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| Language: | English |
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Elsevier
2021-10-01
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| Series: | Engineering |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095809921003258 |
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| author | Ana Montero-Calle Itziar Aranguren-Abeigon María Garranzo-Asensio Carmen Poves María Jesús Fernández-Aceñero Javier Martínez-Useros Rodrigo Sanz Jana Dziaková Javier Rodriguez-Cobos Guillermo Solís-Fernández Eloy Povedano Maria Gamella Rebeca Magnolia Torrente-Rodríguez Miren Alonso-Navarro Vivian de los Ríos J. Ignacio Casal Gemma Domínguez Ana Guzman-Aranguez Alberto Peláez-García José Manuel Pingarrón Susana Campuzano Rodrigo Barderas |
| author_facet | Ana Montero-Calle Itziar Aranguren-Abeigon María Garranzo-Asensio Carmen Poves María Jesús Fernández-Aceñero Javier Martínez-Useros Rodrigo Sanz Jana Dziaková Javier Rodriguez-Cobos Guillermo Solís-Fernández Eloy Povedano Maria Gamella Rebeca Magnolia Torrente-Rodríguez Miren Alonso-Navarro Vivian de los Ríos J. Ignacio Casal Gemma Domínguez Ana Guzman-Aranguez Alberto Peláez-García José Manuel Pingarrón Susana Campuzano Rodrigo Barderas |
| author_sort | Ana Montero-Calle |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. The five-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. |
| first_indexed | 2024-12-14T23:58:06Z |
| format | Article |
| id | doaj.art-37d8fc52650e413c80d384b5a7c4075f |
| institution | Directory Open Access Journal |
| issn | 2095-8099 |
| language | English |
| last_indexed | 2024-12-14T23:58:06Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Engineering |
| spelling | doaj.art-37d8fc52650e413c80d384b5a7c4075f2022-12-21T22:43:01ZengElsevierEngineering2095-80992021-10-0171013931412Multiplexed Biosensing Diagnostic Platforms Detecting Autoantibodies to Tumor-Associated Antigens from Exosomes Released by CRC Cells and Tissue Samples Showed High Diagnostic Ability for Colorectal CancerAna Montero-Calle0Itziar Aranguren-Abeigon1María Garranzo-Asensio2Carmen Poves3María Jesús Fernández-Aceñero4Javier Martínez-Useros5Rodrigo Sanz6Jana Dziaková7Javier Rodriguez-Cobos8Guillermo Solís-Fernández9Eloy Povedano10Maria Gamella11Rebeca Magnolia Torrente-Rodríguez12Miren Alonso-Navarro13Vivian de los Ríos14J. Ignacio Casal15Gemma Domínguez16Ana Guzman-Aranguez17Alberto Peláez-García18José Manuel Pingarrón19Susana Campuzano20Rodrigo Barderas21Chronic Disease Program (UFIEC), Carlos III Health Institute, Madrid E-28220, SpainChronic Disease Program (UFIEC), Carlos III Health Institute, Madrid E-28220, SpainChronic Disease Program (UFIEC), Carlos III Health Institute, Madrid E-28220, Spain; Department of Biochemistry and Molecular Biology, Faculty of Optics and Optometry, Complutense University of Madrid, Madrid E-28040, SpainGastroenterology Unit, San Carlos Clinical Hospital, Madrid E-28040, SpainSurgical Pathology Department, San Carlos Clinical Hospital, Madrid E-28040, SpainTranslational Oncology Division, OncoHealth Institute, Jimenez Diaz Foundation University Hospital, Madrid E-28040, SpainGastroenterology Unit, San Carlos Clinical Hospital, Madrid E-28040, SpainGastroenterology Unit, San Carlos Clinical Hospital, Madrid E-28040, SpainDepartment of Biochemistry, Faculty of Medicine, Alberto Sols Institute of Biomedical Research, CSIC-UAM, Madrid E-28029, SpainChronic Disease Program (UFIEC), Carlos III Health Institute, Madrid E-28220, SpainDepartment of Analytical Chemistry, Faculty of Chemical Sciences, Complutense University of Madrid, Madrid E-28040, SpainDepartment of Analytical Chemistry, Faculty of Chemical Sciences, Complutense University of Madrid, Madrid E-28040, SpainDepartment of Analytical Chemistry, Faculty of Chemical Sciences, Complutense University of Madrid, Madrid E-28040, SpainChronic Disease Program (UFIEC), Carlos III Health Institute, Madrid E-28220, SpainCenter for Biological Research, Spanish National Research Council (CSIC), Madrid, E-28040, SpainCenter for Biological Research, Spanish National Research Council (CSIC), Madrid, E-28040, SpainDepartment of Biochemistry, Faculty of Medicine, Alberto Sols Institute of Biomedical Research, CSIC-UAM, Madrid E-28029, SpainDepartment of Biochemistry and Molecular Biology, Faculty of Optics and Optometry, Complutense University of Madrid, Madrid E-28040, SpainMolecular Pathology and Therapeutic Targets Group, La Paz University Hospital (IdiPAZ), Madrid E-28046, SpainDepartment of Analytical Chemistry, Faculty of Chemical Sciences, Complutense University of Madrid, Madrid E-28040, SpainDepartment of Analytical Chemistry, Faculty of Chemical Sciences, Complutense University of Madrid, Madrid E-28040, SpainChronic Disease Program (UFIEC), Carlos III Health Institute, Madrid E-28220, Spain; Corresponding author.Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. The five-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.http://www.sciencedirect.com/science/article/pii/S2095809921003258AutoantibodiesDiagnosisColorectal cancerExosomesTumor microenviromentHumoral immune response |
| spellingShingle | Ana Montero-Calle Itziar Aranguren-Abeigon María Garranzo-Asensio Carmen Poves María Jesús Fernández-Aceñero Javier Martínez-Useros Rodrigo Sanz Jana Dziaková Javier Rodriguez-Cobos Guillermo Solís-Fernández Eloy Povedano Maria Gamella Rebeca Magnolia Torrente-Rodríguez Miren Alonso-Navarro Vivian de los Ríos J. Ignacio Casal Gemma Domínguez Ana Guzman-Aranguez Alberto Peláez-García José Manuel Pingarrón Susana Campuzano Rodrigo Barderas 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 Autoantibodies Diagnosis Colorectal cancer Exosomes Tumor microenviroment Humoral immune response |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Autoantibodies Diagnosis Colorectal cancer Exosomes Tumor microenviroment Humoral immune response |
| url | http://www.sciencedirect.com/science/article/pii/S2095809921003258 |
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