ABSTRACT: In the past two decades, several methylated DNA targets, including gene promoters and other intronic markers have been explored in tumors and benign lesions. Therefore, it can be expected that a panel of stool-based biomarkers will become a screening method for colorectal cancer (CRC) and adenoma with better sensitivity and specificity, aiming to decrease the incidence and mortality of CRC. In this study, the methylation of secreted frizzled-related protein 1 (SFRP1), hyperplastic polyposis protein 1 (HPP1), α-internexin (INA), Wnt inhibitory factor 1 (WIF1), tissue factor pathway inhibitor 2 (TFPI2), ikaros family zinc finger protein 1 (IKZF1), and spastic paraplegia 20 (SPG20) were detected in stool samples from patients with CRC, adenoma, polyps, and healthy controls, respectively, and these biomarkers were used to establish a logistic regression model for classification. Receiver operating characteristic (ROC) curves were drawn to assess the importance of each biomarker. Subsequently, a biomarker or combination of biomarkers was analyzed for early screening of high-risk neoplasm. The data showed that when a single biomarker was used for CRC screening, the sensitivity ranged from 63.9% to 76.8%, the area under the curve (AUC) ranged from 0.821 to 0.875, and the accuracy ranged from 77.0% to 84.5%. Finally, the methylation of SFRP1, HPP1, TFPI2, and IKZF1 was selected using a backward stepwise method in the multivariate logistic analysis according to the Akaike Information Criterion. These findings indicate that stool DNA biomarkers have good diagnostic power in discriminating high-risk level of neoplasm from healthy population.
