Garranzo-Asensio, MariaRodríguez-Cobos, JavierSan Millán, CoralPoves, CarmenFernández-Aceñero, María JesúsPastor-Morate, DanielViñal, DavidMontero-Calle, Ana MariaSolis-Fernandez, GuillermoCerón, María-ÁngelesGámez-Chiachio, ManuelRodríguez, NuriaGuzmán-Aránguez, AnaBarderas Manchado, RodrigoDomínguez, Gemma2022-11-172022-11-172022-07Mol Oncol. 2022 Jul;16(14):2672-2692.http://hdl.handle.net/20.500.12105/15176Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. Alterations in proteins of the p53-family are a common event in CRC. ΔNp73, a p53-family member, shows oncogenic properties and its effectors are largely unknown. We performed an in-depth proteomics characterization of transcriptional control by ∆Np73 of the secretome of human colon cancer cells and validated its clinical potential. The secretome was analyzed using high-density antibody microarrays and stable isotopic metabolic labeling. Validation was performed by semiquantitative PCR, ELISA, dot-blot and western blot analysis. Evaluation of selected effectors was carried out using 60 plasma samples from CRC patients, individuals carrying premalignant colorectal lesions and colonoscopy-negative controls. In total, 51 dysregulated proteins were observed showing at least 1.5-foldchange in expression. We found an important association between the overexpression of ∆Np73 and effectors related to lymphangiogenesis, vasculogenesis and metastasis, such as brain-derived neurotrophic factor (BDNF) and the putative aminoacyl tRNA synthase complex-interacting multifunctional protein 1 (EMAP-II)-vascular endothelial growth factor C-vascular endothelial growth factor receptor 3 axis. We further demonstrated the usefulness of BDNF as a potential CRC biomarker able to discriminate between CRC patients and premalignant individuals from controls with high sensitivity and specificity.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/ΔNp73 effectorsColorectal cancerIn-depthproteomicsLymphangiogenesisSecretomeColorectal NeoplasmsLymphangiogenesisBrain-Derived Neurotrophic FactorHumansProteomicsTumor Suppressor Protein p53Vascular Endothelial Growth Factor AVascular Endothelial Growth Factor CAttribution-NonCommercial-NoDerivatives 4.0 Internacional3558698916142672-269210.1002/1878-0261.132281878-0261Molecular oncologyopen access