Open AccessIn‐depth proteomics characterization of ∆Np73 effectors identifies key proteins with diagnostic potential implicated in lymphangiogenesis, vasculogenesis and metastasis in colorectal cancer
Author(s) -
GarranzoAsensio María,
RodríguezCobos Javier,
San Millán Coral,
Poves Carmen,
FernándezAceñero María Jesús,
PastorMorate Daniel,
Viñal David,
MonteroCalle Ana,
SolísFernández Guillermo,
Ceron MaríaÁngeles,
GámezChiachio Manuel,
Rodríguez Nuria,
GuzmánAránguez Ana,
Barderas Rodrigo,
Domínguez Gemma
Publication year - 2022
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.13228
Subject(s) - colorectal cancer , lymphangiogenesis , cancer research , metastasis , biology , proteomics , vasculogenesis , cancer , effector , vascular endothelial growth factor , western blot , biomarker , medicine , immunology , endothelial stem cell , genetics , vegf receptors , gene , in vitro
Colorectal 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.