Rodríguez-Cobos Javier, Viñal David, Poves Carmen, Fernández-Aceñero María J, Peinado Héctor, Pastor-Morate Daniel, Prieto Mª Isabel, Barderas Rodrigo, Rodríguez-Salas Nuria, Domínguez Gemma
Department of Biochemistry, Faculty of Medicine, Health Research Institute Alberto Sols CSIC-UAM, IdiPaz, 28029 Madrid, Spain.
Department of Medical Oncology, Hospital Universitario La Paz, CIBERONC, 28046 Madrid, Spain.
Cancers (Basel). 2021 May 7;13(9):2240. doi: 10.3390/cancers13092240.
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 ( = 29), individuals with premalignant lesions ( = 49), and colorectal cancer patients ( = 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.
结直肠癌的早期诊断是患者总体生存的关键因素。实际的筛查方案包括不同方法,但存在显著局限性,如缺乏特异性、侵袭性高以及在疾病晚期才能检测到。源自恶性细胞的细胞外囊泡的特定成分可能代表一种用于结直肠癌早期检测的非侵入性技术。在此,我们研究了健康受试者(n = 29)、癌前病变个体(n = 49)和结直肠癌患者(n = 42)血浆来源的细胞外囊泡中ΔNp73、TAp73和Δ133p53的mRNA水平。癌前病变受试者的细胞外囊泡ΔNp73水平已显著升高。与其他两组相比,结直肠癌患者的Δ133p53水平在统计学上有所增加,且与患者生存相关。值得注意的是,在所有个体中均未检测到TAp73 mRNA。对ΔNp73、Δ133p53和CEA的敏感性、特异性和AUC值的评估支持ΔNp73作为更好的早期诊断生物标志物,而CEA作为识别晚期的最佳标志物。因此,低水平的CEA和高含量的ΔNp73可能在筛查方案中识别出那些有癌前病变高风险的个体。此外,Δ133p53成为结直肠癌中一种潜在的预后生物标志物。