DNA methylation biomarkers for non-invasive diagnostic of Colorectal Cancer
Menée sur plusieurs cohortes de patients, cette étude identifie une signature qui, basée sur la méthylation de l'ADN de trois gènes, pourrait être utile pour le diagnostic précoce d'un cancer colorectal à partir de l'analyse de l'ADN dans des échantillons de selles
DNA methylation biomarkers for non-invasive diagnosis of colorectal cancer (CRC) and precursor lesions have been extensively studied. Different panels have been reported attempting to improve current protocols in clinical practice, although no definite biomarkers have been established. In the present study we have examined patient biopsies starting from a comprehensive analysis of DNA methylation differences between paired normal and tumor samples in known cancer-related genes aiming to select the best performing candidates informative for CRC diagnosis in stool samples. Five selected markers were considered for subsequent analyses in independent biological cohorts and in silico datasets. Among the five selected genes, three of them (AGTR1, WNT2 and SLIT2) were validated in stool DNA of affected patients with a detection sensitivity of 78% (95% CI: 56% - 89%). As a reference, DNA methylation of VIM and SEPT9 was evaluated in a subset of stool samples yielding sensitivities of 55% and 20% respectively. Moreover, our panel may complement histological and endoscopic diagnosis of Inflammatory Bowel Disease (IBD)-associated neoplasia, since it was also efficient detecting aberrant DNA methylation in non-neoplastic tissue samples from affected patients. This novel panel of specific methylation markers can be useful for early diagnosis of CRC using stool DNA, and may help in then follow-up of high risk IBD patients.
Cancer Prevention Research , résumé, 2013