p53 and p63 Proteoforms Derived from Alternative Splicing Possess Differential Seroreactivity in Colorectal Cancer with Distinct Diagnostic Ability from the Canonical Proteins

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dc.contributor.authorMontero Calle, Ana
dc.contributor.authorGarranzo Asensio, María
dc.contributor.authorTorrente Rodríguez, Rebeca Magnolia
dc.contributor.authorRuiz Valdepeñas Montiel, Víctor
dc.contributor.authorPoves, Carmen
dc.contributor.authorDziakova, Jana
dc.contributor.authorSanz, Rodrigo
dc.contributor.authorDíaz Del Arco, Cristina
dc.contributor.authorPingarrón Carrazón, José Manuel
dc.contributor.authorFernández Aceñero, María Jesús
dc.contributor.authorCampuzano Ruiz, Susana
dc.contributor.authorBarderas Manchado, Rodrigo
dc.date.accessioned2024-04-29T12:42:00Z
dc.date.available2024-04-29T12:42:00Z
dc.date.issued2023-03-31
dc.descriptionThe humoral immune response in cancer has been demonstrated to be useful for distinguishing patients from healthy individuals using serum or plasma. Our study aimed to assess whether p53 and p63 proteoforms derived from alternative splicing could have a differential seroreactivity and higher diagnostic value than canonical proteins in colorectal cancer. Using luminescence assays and biosensing approaches with the proteoforms expressed in vitro fused to HaloTag, we demonstrate the appearance of a differential seroreactivity among the proteoforms in colorectal cancer patients. Our findings reveal increased complexity of the humoral immune response in cancer against specific autoantigens, since specific seroreactivity and different diagnostic values were observed among the p53 and p63 proteoforms and the canonical proteins.
dc.description.abstractColorectal cancer (CRC) is the third most common cancer and the second most frequent cause of cancer-related death worldwide. The detection in plasma samples of autoantibodies against specific tumor-associated antigens has been demonstrated to be useful for the early diagnosis of CRC by liquid biopsy. However, new studies related to the humoral immune response in cancer are needed to enable blood-based diagnosis of the disease. Here, our aim was to characterize the humoral immune response associated with the different p53 and p63 proteoforms derived from alternative splicing and previously described as aberrantly expressed in CRC. Thus, here we investigated the diagnostic ability of the twelve p53 proteoforms and the eight p63 proteoforms described to date, and their specific N-terminal and C-terminal end peptides, by means of luminescence HaloTag beads immunoassays. Full-length proteoforms or specific peptides were cloned as HaloTag fusion proteins and their seroreactivity analyzed using plasma from CRC patients at stages I-IV (n = 31), individuals with premalignant lesions (n = 31), and healthy individuals (n = 48). p53γ, Δ40p53β, Δ40p53γ, Δ133p53γ, Δ160p53γ, TAp63α, TAp63δ, ΔNp63α, and ΔNp63δ, together with the specific C-terminal end α and δ p63 peptides, were found to be more seroreactive against plasma from CRC patients and/or individuals with premalignant lesions than from healthy individuals. In addition, ROC (receiver operating characteristic) curves revealed a high diagnostic ability of those p53 and p63 proteoforms to detect CRC and premalignant individuals (AUC higher than 85%). Finally, electrochemical biosensing platforms were employed in POC-like devices to investigate their usefulness for CRC detection using selected p53 and p63 proteoforms. Our results demonstrate not only the potential of these biosensors for the simultaneous analysis of proteoforms’ seroreactivity, but also their convenience and versatility for the clinical detection of CRC by liquid biopsy. In conclusion, we here show that p53 and p63 proteoforms possess differential seroreactivity in CRC patients in comparison to controls, distinctive from canonical proteins, which should improve the diagnostic panels for obtaining a blood-based biomarker signature for CRC detection.
dc.description.departmentDepto. de Química Analítica
dc.description.facultyFac. de Ciencias Químicas
dc.description.fundingtypeDescuento UCM
dc.description.refereedTRUE
dc.description.sponsorshipEuropean Commission
dc.description.sponsorshipMinisterio de Ciencia e Innovación (España)
dc.description.sponsorshipComunidad de Madrid
dc.description.sponsorshipInstituto de Salud Carlos III (España)
dc.description.statuspub
dc.identifier.citationMontero-Calle, A.; Garranzo-Asensio, M.; Torrente-Rodríguez, R.M.; Ruiz-Valdepeñas Montiel, V.; Poves, C.; Dziaková, J.; Sanz, R.; Díaz del Arco, C.; Pingarrón, J.M.; Fernández-Aceñero, M.J.; et al. p53 and p63 Proteoforms Derived from Alternative Splicing Possess Differential Seroreactivity in Colorectal Cancer with Distinct Diagnostic Ability from the Canonical Proteins. Cancers 2023, 15, 2102. https://doi.org/10.3390/ cancers15072102
dc.identifier.doi10.3390/cancers15072102
dc.identifier.issn2072-6694
dc.identifier.officialurlhttps://doi.org/10.3390/cancers15072102
dc.identifier.pmid37046764
dc.identifier.relatedurlhttps://www.mdpi.com/2072-6694/15/7/2102
dc.identifier.urihttps://hdl.handle.net/20.500.14352/103634
dc.issue.number7
dc.journal.titleCancers
dc.language.isoeng
dc.page.final19
dc.page.initial1
dc.publisherMDPI
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/PI20CIII/00019
dc.relation.projectIDinfo:eu-repo/grantAgreement/MICINN/PID2019/103899RB-I00
dc.relation.projectIDinfo:eu-repo/grantAgreement/CAM/TRANSNANOAVANSENS-CMS/2018/NMT-4349
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu543
dc.subject.keywordColorectal cancer
dc.subject.keywordImmunomics
dc.subject.keywordAutoantibodies
dc.subject.keywordp53 family
dc.subject.keywordp53 and p63
dc.subject.keywordAlternative splicing
dc.subject.keywordProteoform
dc.subject.keywordPOC-like device
dc.subject.keywordBiosensor
dc.subject.keywordHumoral immune response
dc.subject.keywordDiagnosis
dc.subject.ucmQuímica analítica (Química)
dc.subject.unesco3201.01 Oncología
dc.subject.unesco2301 Química Analítica
dc.titlep53 and p63 Proteoforms Derived from Alternative Splicing Possess Differential Seroreactivity in Colorectal Cancer with Distinct Diagnostic Ability from the Canonical Proteins
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number15
dspace.entity.typePublication
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