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The specific seroreactivity to ∆Np73 isoforms shows higher diagnostic ability in colorectal cancer patients than the canonical p73 protein

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Garranzo Asensio, María and Guzmán Aránguez, Ana Isabel and Povés Francés, Carmen and Fernández Aceñero, María Jesús and Montero Calle, Ana and Ceron, María Ángeles and Fernández Díez, Servando and Rodríguez Salas, Nuria and Gómez de Cedrón, Marta and Ramírez de Molina, Ana and Domínguez Muñóz, Gemma and Barderas Manchado, Rodrigo (2019) The specific seroreactivity to ∆Np73 isoforms shows higher diagnostic ability in colorectal cancer patients than the canonical p73 protein. Scientific reports, 9 (13547). ISSN 2045-2322

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Official URL: https://doi.org/10.1038/s41598-019-49960-x




Abstract

The p53-family is tightly regulated at transcriptional level. Due to alternative splicing, up to 40 different 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 specific epitopes in ΔNp73 isoforms not present in p73, with several colorectal patients showing unique and specific 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.


Item Type:Article
Uncontrolled Keywords:Diagnostic markers; Tumour biomarkers
Subjects:Medical sciences > Medicine > Biochemistry
Medical sciences > Medicine > Oncology
ID Code:57148
Deposited On:03 Oct 2019 07:28
Last Modified:03 Oct 2019 08:50

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