ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer

The early diagnosis of colorectal cancer is a key factor in the overall survival of the patients. The actual screening programs include different approaches with significant limitations such as unspecificity, high invasiveness, and detection at late stages of the disease. The specific content of ext...

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Main Authors: Javier Rodríguez-Cobos, David Viñal, Carmen Poves, María J. Fernández-Aceñero, Héctor Peinado, Daniel Pastor-Morate, Mª Isabel Prieto, Rodrigo Barderas, Nuria Rodríguez-Salas, Gemma Domínguez
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/9/2240
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author Javier Rodríguez-Cobos
David Viñal
Carmen Poves
María J. Fernández-Aceñero
Héctor Peinado
Daniel Pastor-Morate
Mª Isabel Prieto
Rodrigo Barderas
Nuria Rodríguez-Salas
Gemma Domínguez
author_facet Javier Rodríguez-Cobos
David Viñal
Carmen Poves
María J. Fernández-Aceñero
Héctor Peinado
Daniel Pastor-Morate
Mª Isabel Prieto
Rodrigo Barderas
Nuria Rodríguez-Salas
Gemma Domínguez
author_sort Javier Rodríguez-Cobos
collection DOAJ
description The early diagnosis of colorectal cancer is a key factor in the overall survival of the patients. The actual screening programs include different approaches with significant limitations such as unspecificity, high invasiveness, and detection at late stages of the disease. The specific content of extracellular vesicles derived from malignant cells may represent a non-invasive technique for the early detection of colorectal cancer. Here, we studied the mRNA levels of ΔNp73, TAp73, and Δ133p53 in plasma-derived extracellular vesicles from healthy subjects (<i>n</i> = 29), individuals with premalignant lesions (<i>n</i> = 49), and colorectal cancer patients (<i>n</i> = 42). Extracellular vesicles’ ΔNp73 levels were already significantly high in subjects with premalignant lesions. Δ133p53 levels were statistically increased in colorectal cancer patients compared to the other two groups and were associated with patients’ survival. Remarkably, TAp73 mRNA was not detected in any of the individuals. The evaluation of ΔNp73, Δ133p53 and CEA sensitivity, specificity and AUC values supports ΔNp73 as a better early diagnosis biomarker and CEA as the best to identify advanced stages. Thus, low levels of CEA and a high content of ΔNp73 may identify in screening programs those individuals at higher risk of presenting a premalignant lesion. In addition, Δ133p53 emerges as a potential prognosis biomarker in colorectal cancer.
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spelling doaj.art-fd690a384e8243fc9cf84eb645deaf042023-11-21T18:38:16ZengMDPI AGCancers2072-66942021-05-01139224010.3390/cancers13092240ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal CancerJavier Rodríguez-Cobos0David Viñal1Carmen Poves2María J. Fernández-Aceñero3Héctor Peinado4Daniel Pastor-Morate5Mª Isabel Prieto6Rodrigo Barderas7Nuria Rodríguez-Salas8Gemma Domínguez9Department of Biochemistry, Faculty of Medicine, Health Research Institute Alberto Sols CSIC-UAM, IdiPaz, 28029 Madrid, SpainDepartment of Medical Oncology, Hospital Universitario La Paz, CIBERONC, 28046 Madrid, SpainGastroenterology Unit, Hospital Clínico San Carlos, 28040 Madrid, SpainSurgical Pathology Department, Hospital Gregorio Marañón, 28007 Madrid, SpainMicroenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center, 28029 Madrid, SpainSurgery Department, Hospital Universitario La Paz, 28046 Madrid, SpainSurgery Department, Hospital Universitario La Paz, 28046 Madrid, SpainChronic Disease Programme (UFIEC), Instituto de Salud Carlos III, Majadahonda, 28222 Madrid, SpainDepartment of Medical Oncology, Hospital Universitario La Paz, CIBERONC, 28046 Madrid, SpainDepartment of Biochemistry, Faculty of Medicine, Health Research Institute Alberto Sols CSIC-UAM, IdiPaz, 28029 Madrid, SpainThe early diagnosis of colorectal cancer is a key factor in the overall survival of the patients. The actual screening programs include different approaches with significant limitations such as unspecificity, high invasiveness, and detection at late stages of the disease. The specific content of extracellular vesicles derived from malignant cells may represent a non-invasive technique for the early detection of colorectal cancer. Here, we studied the mRNA levels of ΔNp73, TAp73, and Δ133p53 in plasma-derived extracellular vesicles from healthy subjects (<i>n</i> = 29), individuals with premalignant lesions (<i>n</i> = 49), and colorectal cancer patients (<i>n</i> = 42). Extracellular vesicles’ ΔNp73 levels were already significantly high in subjects with premalignant lesions. Δ133p53 levels were statistically increased in colorectal cancer patients compared to the other two groups and were associated with patients’ survival. Remarkably, TAp73 mRNA was not detected in any of the individuals. The evaluation of ΔNp73, Δ133p53 and CEA sensitivity, specificity and AUC values supports ΔNp73 as a better early diagnosis biomarker and CEA as the best to identify advanced stages. Thus, low levels of CEA and a high content of ΔNp73 may identify in screening programs those individuals at higher risk of presenting a premalignant lesion. In addition, Δ133p53 emerges as a potential prognosis biomarker in colorectal cancer.https://www.mdpi.com/2072-6694/13/9/2240ΔNp73TAp73Δ133p53colorectal cancerextracellular vesiclesliquid biopsy
spellingShingle Javier Rodríguez-Cobos
David Viñal
Carmen Poves
María J. Fernández-Aceñero
Héctor Peinado
Daniel Pastor-Morate
Mª Isabel Prieto
Rodrigo Barderas
Nuria Rodríguez-Salas
Gemma Domínguez
ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer
Cancers
ΔNp73
TAp73
Δ133p53
colorectal cancer
extracellular vesicles
liquid biopsy
title ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer
title_full ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer
title_fullStr ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer
title_full_unstemmed ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer
title_short ΔNp73, TAp73 and Δ133p53 Extracellular Vesicle Cargo as Early Diagnosis Markers in Colorectal Cancer
title_sort δnp73 tap73 and δ133p53 extracellular vesicle cargo as early diagnosis markers in colorectal cancer
topic ΔNp73
TAp73
Δ133p53
colorectal cancer
extracellular vesicles
liquid biopsy
url https://www.mdpi.com/2072-6694/13/9/2240
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