DNA Methylation Biomarkers for Noninvasive Diagnosis of Colorectal Cancer

TLDR

DNA methylation biomarkers have been extensively studied for noninvasive colorectal cancer diagnosis, yet no definitive panel has been established. This study aimed to identify the most effective DNA methylation markers for CRC detection in stool samples. Researchers performed a comprehensive comparison of methylation differences between paired normal and tumor tissues in known cancer‑related genes, selecting five candidate markers for validation in independent cohorts and in silico datasets. Three markers (AGTR1, WNT2, SLIT2) achieved 78 % sensitivity (95 % CI 56–89 %) in stool DNA, outperforming VIM and SEPT9, and the panel also detected aberrant methylation in non‑neoplastic IBD tissue, suggesting utility for early CRC diagnosis and high‑risk IBD follow‑up.

Abstract

DNA methylation biomarkers for noninvasive 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 biologic cohorts and in silico data sets. 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% confidence interval (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 histologic and endoscopic diagnosis of inflammatory bowel disease (IBD)-associated neoplasia, as 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 the follow-up of high-risk patients with IBD.