Combined detection of stool-based methylation indicators for early screening of colorectal neoplasm

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.