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The specific seroreactivity to ∆Np73 isoforms shows higher diagnostic ability in colorectal cancer patients than the canonical p73 protein
- Source :
- Biblos-e Archivo. Repositorio Institucional de la UAM, instname, Digital.CSIC. Repositorio Institucional del CSIC, Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019), Scientific Reports, E-Prints Complutense. Archivo Institucional de la UCM, E-Prints Complutense: Archivo Institucional de la UCM, Universidad Complutense de Madrid, Repisalud, Instituto de Salud Carlos III (ISCIII)
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- © The Author(s) 2019.<br />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.<br />This work was supported by the Ramon y Cajal programme of the MINECO and the financial support of the PI17CIII/00045 grant from the AES-ISCIII program to R.B., cofounded by FEDER funds. G.D. acknowledges the financial support of PI15/00246 grant of the FIS and Cátedra UAM-Roche en Medicina de Innovación. M.G-A. was supported by a contract of the Programa Operativo de Empleo Juvenil y 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. We thank the excellent technical support of Maricruz Sánchez. A.M-C. is a recipient of a FPU fellowship from the Ministerio de Educación, Cultura y Deporte.
- Subjects :
- Male
0301 basic medicine
Colorectal cancer
lcsh:Medicine
Epitope
Oncología
Tumour biomarkers
0302 clinical medicine
Protein Isoforms
Genes, Tumor Suppressor
colorectal cancer patients
lcsh:Science
Aged, 80 and over
Multidisciplinary
Nuclear Proteins
Middle Aged
DNA-Binding Proteins
030220 oncology & carcinogenesis
Female
Colorectal Neoplasms
Bioquímica
Adult
Transcriptional Activation
Gene isoform
Medicina
Biology
Article
03 medical and health sciences
Immune system
medicine
Humans
Serologic Tests
Gene
Aged
Tumor Suppressor Proteins
lcsh:R
Alternative splicing
Autoantibody
Cancer
Tumor Protein p73
Diagnostic markers
Genes, p53
medicine.disease
Alternative Splicing
030104 developmental biology
Trans-Activators
Cancer research
lcsh:Q
Tumor Suppressor Protein p53
Transcription Factors
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....59cf63cbb23ce6486c56bf6d9096f2f0