The specifc seroreactivity to ∆Np73 isoforms shows higher diagnostic ability in colorectal cancer patients than the canonical p73 protein
Entity
UAM. Departamento de MedicinaPublisher
Nature Research (part of Springer Nature)Date
2019-09-19Citation
10.1038/s41598-019-49960-x
Scientific Reports 9 (2019): 13547
ISSN
2045-2322DOI
10.1038/s41598-019-49960-xFunded by
Tis work was supported by the Ramon y Cajal programme of the MINECO and the fnancial support of the PI17CIII/00045 grant from the AES-ISCIII program to R.B., cofounded by FEDER funds. G.D. acknowledges the fnancial support of PI15/00246 grant of the FIS and Cátedra UAM-Roche en Medicina de InnovaciónProject
Gobierno de España. PI17CIII/00045; Gobierno de España. PI15/00246Editor's Version
https://doi.org/10.1038/s41598-019-49960-xSubjects
colorectal cancer patients; MedicinaRights
© The Author(s) 2019Abstract
The p53-family is tightly regulated at transcriptional level. Due to alternative splicing, up to 40
diferent theoretical proteoforms have been described for p73 and at least 20 and 10 for p53 and
p63, respectively. However, only the canonical proteins have been evaluated as autoantibody
targets in cancer patients for diagnosis. In this study, we have cloned and expressed in vitro the most
upregulated proteoforms of p73, ΔNp73α and ΔNp73β, for the analysis of their seroreactivity by a
developed luminescence based immunoassay test using 145 individual plasma from colorectal cancer,
premalignant individuals and healthy controls. ∆Np73α seroreactivity showed the highest diagnostic
ability to discriminate between groups. The combination of ∆Np73α, ∆Np73β and p73 proteoforms
seroreactivity were able to improve their individual diagnostic ability. Competitive inhibition
experiments further demonstrated the presence of unique specifc epitopes in ΔNp73 isoforms not
present in p73, with several colorectal patients showing unique and specifc seroreactivity to the
ΔNp73 proteoforms. Overall, we have increased the complexity of the humoral immune response to
the p53-family in cancer patients, showing that the proteoforms derived from the alternative splicing of
p73 possess a higher diagnostic ability than the canonical protein, which might be extensive for p53 and
p63 proteins
Files in this item
Google Scholar:Garranzo-Asensio, María
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Guzmán-Aranguez, Ana
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Povés, Carmen
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Fernández-Aceñero, María Jesús
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Montero-Calle, Ana
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Ceron, María Angeles
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Fernandez-Diez, Servando
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Rodríguez, Nuria
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Gómez de Cedrón, Marta
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Ramírez de Molina, Ana
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Domínguez Muñoz, Gemma
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Barderas, Rodrigo
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