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

Simple Summary The survival of colorectal cancer patients largely relies on the stage at diagnosis. The identification of early and non-invasive biomarkers to be used in screening programs for the diagnosis of the disease at the premalignant stage is mandatory. The aim of this study is to validate in plasma-derived extracellular vesicles secreted by malignant cells the diagnostic potential of well-known tumor-associated genes, Delta Np73, TAp73, and Delta 133p53, in healthy subjects (n = 29), individuals with premalignant lesions (n = 49), and colorectal cancer patients (n = 42). Our data support Delta Np73 levels contained in extracellular vesicles as such a non-invasive and premature biomarker for the early diagnosis of 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 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 Delta Np73, TAp73, and Delta 133p53 in plasma-derived extracellular vesicles from healthy subjects (n = 29), individuals with premalignant lesions (n = 49), and colorectal cancer patients (n = 42). Extracellular vesicles' Delta Np73 levels were already significantly high in subjects with premalignant lesions. Delta 133p53 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 Delta Np73, Delta 133p53 and CEA sensitivity, specificity and AUC values supports Delta Np73 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 Delta Np73 may identify in screening programs those individuals at higher risk of presenting a premalignant lesion. In addition, Delta 133p53 emerges as a potential prognosis biomarker in colorectal cancer.